Paclobutrazol Human Health Risk Assessment DP No. D394230 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

Date: September 11, 2013 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

SUBJECT: Paclobutrazol: Preliminary Human Health Risk Assessment for Registration 

Review 

PC Code: 125601 

Decision No.: 455061 

Petition No.: 

Risk Assessment Type: Single 

Chemical/ Aggregate 

TXRNo.: 

MRID No.: 45310801,45336601,45214201 

DP Barcode: D394230 

Registration No.: 

Regulatory Action: Registration Review 

Case No.: 7002 

CAS No.: 76738-62-0 

40 CFR: 

FROM: Monica Hawkins, Ph.D., M.P.H., Environmental H~~ h Sf.ie~f t ~/ ( j) 

Nancy McCarroll, Ph.D., Gencll. ticis :roxicologjst ~~~ llteu .J~ Sheila Piper, Senior Chemist uC!.JJo~:{j.-6-- . Risk Assessment Branch VI 

and 

Charles Smith, Chief 

Risk Assessment Branc...._._~ 

Health Effects Division (7509P) /7 

THROUGH: FeleciaFort, Chief --. d& t1--f Risk Assessment Branch VI 

Health Effects Division 

TO: K.hue Nguyen 

Risk Management and Implementation Branch I 

Pesticide Re-evaluation Division (7508P) 

Page I of 58 
Paclobutrazol Human Health Risk Assessment DP No. D394230 

The Health Effects Division (HED) of the Office of Pesticide Programs (OPP) is charged with 

estimating the risk to human health from exposure to pesticides. As part of Registration Review) 

the Pesticide Re-evaluation Division (PRD) of OPP has requested that HED evaluate the hazard 

and exposure data and conduct dietary, occupational, residential, and aggregate exposure 

assessments, as needed, to estimate the risk to human health that will result from the registered 

uses of paclobutrazol. 

HED has evaluated the toxicity and exposure databases for the active ingredient, paclobutrazol, 

and has conducted a human health risk assessment in support of Registration Review. Based on 

this assessment, HED has determined that there are potential risk estimates of concern for the 

currently registered uses of paclobutrazol. 

A summary of the findings and an assessment of human health risk resulting from the currently 

registered uses of paclobutrazol are provided in this document. The HED team members 

contributing to this risk assessment include Charles Smith (risk assessment), Monica Hawkins 

(occupational and residential assessment), Nancy McCaroll (hazard assessment), and Sheila 

Piper (chemistry assessment). Faruque Khan of the Environmental Fate and Effects Division 

(EFED) performed the drinking water assessment for paclobutrazol. 

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Paclobutrazol Human Health Risk Assessment DP No. D394230

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1.0 Executive Summary................................................................................................................... 5

2.0 Ingredient Profile ....................................................................................................................... 8

2.1 Structure and Nomenclature................................................................................................... 8

2.2 Physical/Chemical Characteristics......................................................................................... 8

2.3 Summary of Existing Uses..................................................................................................... 9

2.4 Anticipated Exposure Pathways........................................................................................... 10

2.5 Consideration of Environmental Justice .............................................................................. 10

3.0 Hazard Characterization and Dose-Response Assessment...................................................... 10

3.1 Toxicology Studies Available for Analysis ......................................................................... 10

3.2 Absorption, Distribution, Metabolism and Elimination (ADME) ....................................... 11

3.3 Toxicological Profile............................................................................................................ 12

3.4 Consideration of Toxicity to Children ................................................................................. 12

3.4.1 Completeness of the Toxicology Database................................................................... 12

3.4.2 Evidence of Neurotoxicity ............................................................................................ 13

3.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal ............... 13

3.4.4 Residual Uncertainty in the Exposure Database........................................................... 14

3.5 Toxicity Endpoint and Point of Departure Selections.......................................................... 14

3.5.1 Dose-Response Assessment.......................................................................................... 14

3.5.2 Recommendation for Combining Routes of Exposure for Risk Assessment ............... 15

3.5.3 Cancer Classification and Risk Assessment Recommendations .................................. 15

3.6 Endocrine Disruption ........................................................................................................... 17

4.0 Dietary Exposure and Risk Assessment .................................................................................. 17

4.1 Summary of Environmental Degradation ............................................................................ 17

4.2 Food Residue Profile............................................................................................................ 18

4.3 Water Residue Profile .......................................................................................................... 18

4.4 Dietary Risk Assessment...................................................................................................... 19

4.4.1 Acute Dietary Risk Assessment.................................................................................... 19

4.4.2 Chronic Dietary Risk Assessment ................................................................................ 19

4.4.3 Cancer Dietary Risk Assessment.................................................................................. 19

4.4.4 Dietary Risk Assessment Summary Table.................................................................... 20

5.0 Residential (Non-Occupational) Exposure/Risk Characterization .......................................... 20

5.1 Residential Handler Exposure and Risk............................................................................... 20

5.2 Residential Postapplication Exposure and Risk................................................................... 21

5.3 Combined Residential Risk Estimates................................................................................. 24

6.0 Aggregate Exposure/Risk Characterization............................................................................. 26

6.1 Acute Aggregate Risk .......................................................................................................... 26

6.2 Short- and Intermediate-Term Aggregate Risk.................................................................... 26

6.3 Chronic Aggregate Risk....................................................................................................... 27

6.4 Cancer Aggregate Risk......................................................................................................... 27

6.5 Updated Aggregate Assessment of Free Triazole & its Conjugates.................................... 27

7.0 Cumulative Exposure/Risk Characterization........................................................................... 29

8.0 Occupational Exposure/Risk Characterization ........................................................................ 29

8.1 Short-/Intermediate-Term Handler Risk .............................................................................. 29

8.1.1 Short-/Intermediate-Term Handler Risk for Turf, Ornamental, and Tree Uses ........... 29

8.1.2 Short-/Intermediate-Term Handler Risk for Seed Treatments...................................... 33

8.2 Occupational Post-Application Exposure and Risk ............................................................. 37
Paclobutrazol Human Health Risk Assessment DP No. D394230

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9.0 References................................................................................................................................ 39

Appendix A: Paclobutrazol Toxicity Profiles..................................................................................... 40

Appendix B: Review of Human Research .......................................................................................... 57

Appendix C: Physical and Chemical Properties................................................................................. 58
Paclobutrazol Human Health Risk Assessment DP No. D394230

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1.0 Executive Summary

As part of Registration Review, the Pesticide Re-evaluation Division (PRD) of the Office of 

Pesticide Programs (OPP) has requested that the Health Effects Division (HED) evaluate the 

hazard and exposure data and conduct dietary (drinking water only), occupational, residential, 

and aggregate exposure assessments, as needed, to estimate the risk to human health that will 

result from the registered uses of paclobutrazol. A summary of the findings and an assessment 

of human health risk resulting from the currently registered uses of paclobutrazol are provided in 

this document.

Use Profile: Paclobutrazol (αR,βR)-rel-β-[(4-chlorophenyl)methyl]-α-(1,1-dimethylethyl)-1H1,2,4-triazole-1-ethanol is a triazole plant growth regulator. There are a number of currently 

registered labels for paclobutrazol with formulations including liquids, wettable powders, and 

granulars. It is currently registered for use as a foliar spray for turf (including parks, athletic 

fields, residential lawns, and golf courses); a foliar spray for ornamentals in greenhouses and 

nurseries; as a tree injection; as a tree root drench; and as a seed treatment. There are currently 

no registered food uses for paclobutrazol.

Hazard Assessment: The studies available for consideration of paclobutrazol toxicity provide a 

comprehensive database; however, there are three outstanding studies according to revised 40 

CFR Part 158 Toxicology Data Requirement. These studies include an acute neurotoxicity

(ACN) study, a subchronic neurotoxicity (SCN) study, and an immunotoxicity study (D. Smegal, 

TXR0056149, 01/03/12). The registrants have recently submitted the final ACN study report to 

the Agency. The Agency plans to review and incorporate the ACN into the revised Registration 

Review risk assessment. In addition, as specified in the 2012 HASPOC memo, the Agency will 

reevaluate the need for an SCN based on the results of the ACN. Consistent with current Agency 

policies, the need for an immunotoxicity study will also be reevaluated at that time.

In subchronic feeding studies in rats and dogs, the target organ was the liver, based on increased 

organ weights and alterations in clinical chemistry parameters associated with liver function. In 

agreement with the subchronic findings, the liver was the target organ following chronic 

exposure via the diet in dogs, rats, and mice. Adverse effects consisted of: increased liver 

weights, steatosis, and/or alterations in clinical chemistry parameters associated with liver 

function. 

A 21-day dermal study in rabbits showed a dose-related increase in the degree of hyperkeratosis, 

acanthosis, and inflammatory changes of the superficial dermis at higher doses. These effects 

are, however, local and no systemic effects were seen in the study.

Two pre-natal developmental toxicity studies were available. In one study, there was evidence 

for increased qualitative susceptibility where developmental effects, in the form of delayed 

ossification and cleft palates, were seen at a maternally toxic dose. In another study, there was 

evidence for quantitative susceptibility; developmental effects characterized as renal dilation, 

hydrouretar minor skeletal defects were seen in the absence of maternal toxicity. There was no 

evidence (quantitative or qualitative) of increased susceptibility was seen following in utero 
Paclobutrazol Human Health Risk Assessment DP No. D394230

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exposures to rabbit or following pre-and/or post natal exposure in rats for two generations in the 

reproduction study. 

Food Quality Protection Act (FQPA) considerations do not apply to paclobutrazol as the 

currently registered use patterns are all non-food uses. However, acute and subchronic 

neurotoxicity studies are required since paclobutrazol is a member of the triazole chemical class

which in general appear to be neurotoxic and there is not sufficient data that evaluated the 

neurotoxic potential of paclobutrazol. Consequently, the default 10X database uncertainty factor 

(UFDB) has been retained for the lack of these studies. The Agency will reconsider this database 

uncertainty factor after the review of the recently submitted ACN study is completed.

Following chronic dietary administration to mice, rats and dogs, the liver was the target organ for 

paclobutrazol-induced toxicity. Liver toxicity manifested as alteration in hepatic enzymes, 

changes in liver weights and histopathological lesions in all three species.

Carcinogenicity studies are not required for non-food use chemicals. Carcinogenicity studies in 

mice and rats are available; however, the Agency was unable to determine the potential 

carcinogenicity of paclobutrazol because the maximum tolerated dose (MTD) was not achieved 

in the 2-year carcinogenicity/chronic study in rats and the carcinogenicity/chronic study in mice.

The carcinogenic potential of paclobutrazol will be re-evaluated if the use pattern changes (i.e., 

food uses are proposed). 

Food Residue Profile: There are no proposed or currently registered food uses for 

paclobutrazol.

Drinking Water Profile: Paclobutrazol is a highly to moderately mobile chemical that is 

expected to be fairly persistent in the environment. Based on the environmental fate parameters, 

there is the potential for paclobutrazol to reach drinking water resources. The Environmental 

Fate and Effects Division (EFED) performed Tier 1 surface water and groundwater modeling. 

The results of this modeling were incorporated into the paclobutrazol dietary assessment.

Dietary Exposure and Risk: Although there are no registered food uses for paclobutrazol, 

dietary exposure is possible via drinking water. An acute dietary (drinking water only) exposure 

assessment was not performed as no appropriate endpoints were identified from the available 

paclobutrazol toxicity studies for the acute dietary scenario. A chronic dietary (drinking water

only) exposure assessment was performed that directly incorporated potential drinking water 

residues. The chronic dietary risk estimates are below HED’s level of concern for all population 

subgroups, including those comprised of infants and children.

Residential Exposure: Residential handler exposures to the existing uses of paclobutrazol may 

occur to adults via the dermal and inhalation route. All residential handler dermal exposure 

scenarios do not exceed HED’s level of concern (MOEs ≥ 1000) except for 

mixing/loading/applying with a belly grinder (MOE = 790).

Residential postapplication exposures to the existing uses of paclobutrazol may occur via the 

dermal and oral (non-dietary ingestion) route. Dermal post-application risks were assessed for 
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adults and children 1 < 2 years old while oral post-application risks were assessed for children 1 

< 2 years old. All adult and children mowing and golfing dermal risk estimates for both liquid 

and granular formulations do not exceed HED’s level of concern (MOEs ≥ 1000). All adult and 

children playing on treated turf dermal risk estimates for both liquid and granular formulations 

exceed HED’s level of concern (MOEs ≥ 1000). All children 1 < 2 years old oral non-dietary 

ingestion risk estimates for both liquid and granular formulations do not exceed HED’s level of 

concern (MOEs ≥ 1000).

Aggregate Risk: An acute aggregate assessment was not performed as no appropriate endpoints 

were identified from the available paclobutrazol toxicity studies for the acute dietary (drinking

water only) scenario. The chronic aggregate risk estimates are equivalent to the corresponding 

dietary risk estimates, which are not of concern. The short- and intermediate-term toxicological 

endpoints for paclobutrazol are the same. As a result, for residential exposure scenarios, only 

short-term exposures were assessed. Chronic dietary exposure is considered to be a background 

exposure level to which the adult and children short-term residential exposures are added. All of 

the adult and children 1 < 2 years old chronic dietary + dermal aggregate risk estimates exceed 

HED’s level of concern (MOEs ≤ 1000) while all of the children 1 < 2 years old chronic dietary 

+ hand-to-mouth aggregate risk estimates do not exceed HED’s level of concern (MOEs ≥ 1000).

Occupational Exposure/Risk: Occupational handler exposures to the existing turf, ornamental, 

and tree uses of paclobutrazol may occur via the dermal and inhalation route. The short- and 

intermediate-term risk estimates for most occupational handler scenarios do not exceed HED’s 

level of concern (MOEs > 1000) at some level of personal protective equipment (PPE). 

However, there are some handheld equipment scenarios that exceed HED’s level of concern 

(MOEs < 1000) even with the use of PPE.

Occupational handler exposures to the existing seed uses of paclobutrazol may occur via the 

dermal and inhalation route for both primary handlers (i.e., those who treat the seed in 

commercial seed treatment facilities) and secondary handlers (i.e., those who plant paclobutrazol 

treated seeds). The short- and intermediate-term risk estimates for all primary and secondary 

handler scenarios do not exceed HED’s level of concern (MOEs > 1000) at some level of 

personal protective equipment (PPE).

Occupational postapplication exposures to the existing uses of paclobutrazol may occur via the 

dermal route. The short- and intermediate-term risk estimates for all occupational 

postapplication activities do not exceed HED’s level of concern (MOEs > 1000) except for hand 

set irrigation in nurseries. The restricted entry interval (REI) listed on the existing paclobutrazol 

labels is based on the acute toxicity of the technical material. Paclobutrazol is classified as 

Toxicity Category II for acute dermal toxicity and Toxicity Category III for eye and skin 

irritation. In accordance with the Worker Protection Standard (WPS), acute Toxicity Category 

III and II chemicals require a 24- or 12- hour REI, respectively. Based on the acute dermal 

toxicity, the 12-hour REI that appears on the current paclobutrazol labels may not be adequate

and should be revisited. Special consideration should also be given to use of hand set irrigation 

in nurseries.
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Review of Human Research: This risk assessment relies in part on data from studies in which 

adult human subjects were intentionally exposed to a pesticide or other chemical. These studies 

(listed in Appendix B) have been determined to require a review of their ethical conduct and all 

of the studies utilized in this assessment have received the appropriate review.

2.0 Ingredient Profile

Paclobutrazol is a triazole plant growth regulator with a number of currently registered products.

2.1 Structure and Nomenclature

Table 2.1: Flumethrin Nomenclature

Chemical Structure

Common Name Paclobutrazol

IUPAC name (2RS,3RS)-1-(4-chlorophenyl)-4,4-dimethyl-2-(1H-1,2,4-triazol-1-yl)pentan-3-ol

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

ethanol

CAS Registry Number 76738-62-0

Chemical Class Triazole plant growth regulator

2.2 Physical/Chemical Characteristics

The physical and chemical properties, as well as a summary of relevant environmental fate 

parameters are detailed in Appendix C.

Paclobutrazol’s vapor pressure (1.28 x 10-9mm Hg @ 25.0°C) and Henry's Law Constant (8.09 x 

10-10 atm m3/mol) indicate that the compound is relatively non-volatile under field conditions. 

The log Kow of 3.2 indicates the potential for this chemical to bioaccumulate in aquatic 

organisms. Paclobutrazol has a low solubility (25.9 mg/L) in water; however, paclobutrazol is a 

highly to moderately mobile chemical that is expected to be fairly persistent in the environment. 

Based on the use pattern and environmental fate parameters, there is the potential for 

paclobutrazol to reach water resources. 
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2.3 Summary of Existing Uses

There are a number of currently registered labels for paclobutrazol including liquid, wettable 

powder, and granular formulations. It is currently registered for use as a foliar spray for turf 

(including parks, athletic fields, residential lawns, and golf courses); a foliar spray for 

ornamentals in greenhouses and nurseries; as a tree injection; as a tree root drench; and as a seed 

treatment. Table 2.3 provides more detail related to the currently registered uses of 

paclobutrazol.

Table 2.3: Paclobutrazol Use Patterns and Formulations

Formulation Use Sites Maximum 

Application Rate

Application 

Equipment REI Notes

Soluble 

Concentrate Turf 0.75 lb ai/A Ground and handheld

24 hrs or 12 

hrs depending 

on label

Although paclobutrazol turf 

products do not appear to be 

specifically marketed towards 

residential handler use (i.e., 

homeowners); residential handler 

use was assumed to be protective 

of any such use

Granular Turf 0.5 lb ai/A Ground and 

handheld 12 hrs

Although paclobutrazol turf 

products do not appear to be 

specifically marketed towards 

residential handler use (i.e., 

homeowners); residential handler 

use was assumed to be protective 

of any such use

Soluble 

Concentrate

Tree Injection 

(Soil injection at 

base of tree)

0.352 lb ai/tree Soil injection 

equipment N/A

Emulsifiable 

Concentrate

Pre-plant 

plugs/liners 0.0000051 lb ai/gal Plug/liner soak N/A

Emulsifiable 

Concentrate Bulbs 0.00255 lb ai/gal Bulb soak N/A

Application rate represents 

highest application rate for a 

bulb (freesia)

Emulsifiable 

Concentrate

Ornamental 

Plants in 

Greenhouses 

and Nurseries

0.59 lb ai/A Ground and 

handheld 12 hours

Application rate represents 

highest application rate for an 

ornamental (chrysanthemums)

Soluble 

Concentrate

Tree Injection

(8 inch tree) 0.0099 lb ai/tree Pressurized injection system

N/A

Application rates on labels are 

presented for multiple diameter 

trees; two application rates were 

selected to be representative of 

those on the labels

Tree Injection 

(35 inch tree) 0.07 lb ai/tree Pressurized injection system

Soluble 

Concentrate

Cucurbit Seed 0.00027 lb ai/lb seed

Commercial seed 

treatment equipment N/A On-farm seed treatment is prohibited

Tomato Seed 0.00414 lb ai/lb seed

Pepper Seed 0.00247 lb ai/lb seed

Broccoli Seed 0.000661 lb ai/lb seed

Cauliflower

Seed 0.000635 lb ai/lb seed

Cabbage Seed 0.000639 lb ai/lb seed

Wettable

Powder

Tree Injection 

(6-16 inches in 

diameter)

0.000059 lb ai/tree Pressurized 

injection system

N/A

Application rates on labels are 

presented for multiple diameter 

trees; two application rates were 

selected to be representative of 

those on the labels

Tree Injection 

(>16 inches in 

diameter)

0.00024 lb ai/tree Pressurized 

injection system
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2.4 Anticipated Exposure Pathways

Humans are not expected to be exposed to paclobutrazol via food as the existing uses of 

paclobutrazol are all considered to be non-food uses. Drinking water exposure is expected based 

on the existing use pattern and environmental fate parameters of paclobutrazol. The existing 

uses will also potentially result in residential handler and post-application exposures. 

Additionally, there is a potential for occupational handler and post-application exposures.

2.5 Consideration of Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, were considered in this 

human health risk assessment, in accordance with U.S. Executive Order 12898, “Federal Actions 

to Address Environmental Justice in Minority Populations and Low-Income Populations,” 

(http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf. As a part of every pesticide risk 

assessment, OPP considers a large variety of consumer subgroups according to well-established 

procedures. In line with OPP policy, HED estimates risks to population subgroups from 

pesticide exposures that are based on patterns of that subgroup’s food and water consumption, 

and activities in and around the home that involve pesticide use in a residential setting. 

Extensive data on food consumption patterns are compiled by the USDA under the Continuing 

Survey of Food Intake by Individuals (CSFII) and are used in pesticide risk assessments for all 

registered food uses of a pesticide. These data are analyzed and categorized by subgroups based 

on age, season of the year, ethnic group, and region of the country. Additionally, OPP is able to 

assess dietary exposure to smaller, specialized subgroups and exposure assessments are 

performed when conditions or circumstances warrant. Whenever appropriate, non-dietary 

exposures based on home use of pesticide products and associated risks for adult applicators and 

for toddlers, youths, and adults entering or playing on treated areas postapplication are evaluated. 

Further considerations are currently in development as OPP has committed resources and 

expertise to the development of specialized software and models that consider exposure to 

bystanders and farm workers as well as lifestyle and traditional dietary patterns among specific 

subgroups.

3.0 Hazard Characterization and Dose-Response Assessment

3.1 Toxicology Studies Available for Analysis

The studies available for consideration of paclobutrazol toxicity provide a comprehensive 

database; however, there are three outstanding studies according to revised 40 CFR Part 158 

Toxicology Data Requirement. These studies include an acute neurotoxicity study, a subchronic 

neurotoxicity study, and an immunotoxicity study (D. Smegal, TXR0056149, 01/03/12). The 

registrants have recently submitted the final ACN study report to the Agency. The Agency plans 

to review and incorporate the ACN into the revised Registration Review risk assessment. In 

addition, as specified in the 2012 HASPOC memo, the Agency will reevaluate the need for an 

SCN based on the results of the ACN. Consistent with current Agency policies, the need for an 

immunotoxicity study will also be reevaluated at that time. Data requirements for the non-food 

uses of paclobutrazol are listed in Table A.1 in Appendix A. The data from the following studies 

were used to evaluate the hazard potential of paclobutrazol (see Appendix A: Tables A.2 and

A.3): 
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Acute lethality studies (oral, dermal, inhalation, primary eye and dermal irritation, 

and dermal sensitization)

Subchronic oral toxicity studies [rat (with supplemental data) and dog) 

Developmental (2 rat and 2 rabbit) and reproductive toxicity (rat) studies (with 

supplemental data)

Dermal toxicity (21-day dermal toxicity in rabbits)

Chronic oral toxicity studies (rat and dog)

Carcinogenicity studies [rat [chronic combined, with supplemental data) and 

mouse]

Metabolism studies (rat and dog)

Mutagenicity battery 

Paclobutrazol hazard was last reviewed by HED’s RfD/Peer Review Committee in 1994 (Memo, G. 

Ghali, 6/21/94). New data have been submitted since that review was completed. The registrant 

submitted a number of pieces of supplemental data (MRID 47338506) related to the 2-generation 

reproduction study. These data include the following: individual pup clinical observational 

signs; historical control data for these observations; and data for achieved dietary levels based on 

nominal dietary concentrations, food consumption, and body weight. Additional data for 

achieved dietary levels were also received for the 90-day feeding study in rats and for the 2-year 

chronic feeding study in rats (MRID 47078901). These supplemental data have recently been 

reviewed (TXR. No.0056158). The risk assessment team has incorporated these data into this risk 

assessment and reevaluated the points of departure and toxicity endpoints for the occupational and 

residential scenarios using current policies on selecting endpoints and uncertainty factors.

3.2 Absorption, Distribution, Metabolism and Elimination (ADME)

Rats and dogs readily absorb low and high oral doses of paclobutrazol and excretion is rapid (70 

to 80% of paclobutrazol is excreted within 72 hours). The major route of excretion is the urine 

but it is still present in the liver, kidneys, and gastrointestinal tract mostly as the parent 

compound after 72 hours. Paclobutrazol is included in the triazole alanine group of triazole 

derivatives. However, findings from a rat metabolism study indicate that the diol and carboxylic 

acid analogues of paclobutrazol are the major metabolites and that no triazole alanine was found. 

3.2.1 Dermal Absorption

A dermal penetration study in rats (MRID 41048202) was available for paclobutrazol in which 

male rats were dermally exposed on an area of 10 cm2 /rat. The highest percentage of the 

absorbed dose and the remaining dose on the washed application site for exposures of 10 and 24 

hours were: 0.011 mg/rat: total absorbed dose (after 10 hours) = 15.1%; total absorbed dose 

(after 24 hours) = 24.5%. For risk assessment purposes, HED is using the conservative 

assumption that the dermal absorption of paclobutrazol is 24.5%.
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3.3 Toxicological Profile

In subchronic feeding studies in rats and dogs, the target organ was the liver, based on increased 

organ weights and alterations in clinical chemistry parameters associated with liver function. In 

agreement with the subchronic findings, the liver was the target organ following chronic 

exposure via the diet in dogs, rats, and mice. Adverse effects consisted of: increased liver 

weights, steatosis, and/or alterations in clinical chemistry parameters associated with liver 

function. 

A 21-day dermal study in rabbits showed a dose-related increase in the degree of hyperkeratosis, 

acanthosis, and inflammatory changes of the superficial dermis at higher doses. These effects 

are, however, local and no systemic effects were seen in the study.

Two pre-natal developmental toxicity studies were available. In one study, there was evidence 

for increased qualitative susceptibility where developmental effects, in the form of delayed 

ossification and cleft palates, were seen at a maternally toxic dose. In another study, there was 

evidence for quantitative susceptibility; developmental effects characterized as renal dilation, 

hydrouretar minor skeletal defects were seen in the absence of maternal toxicity. There was no 

evidence (quantitative or qualitative) of increased susceptibility was seen following in utero 

exposures to rabbit or following pre-and/or post natal exposure in rats for two generations in the 

reproduction study. 

Paclobutrazol has low toxicity in the rat, rabbit, and guinea pig via the oral (category III) route of 

exposure. It is moderately toxic via the dermal route (category II) in rats and rabbits and via the 

inhalation route (category II) in rats. It is moderately irritating to the skin and the eye and is 

negative for dermal sensitization. 

3.4 Consideration of Toxicity to Children

Food Quality Protection Act (FQPA) considerations do not apply to paclobutrazol as the 

currently registered use patterns are all non-food uses. However, there are potential exposures to 

infants and children from the residential uses of paclobutrazol. There are adequate pre-and/or 

post natal toxicity studies that demonstrated no residual uncertainties to infants and children for 

pre and/or post natal susceptibility. The PODs used for assessing risks to infants and children 

from dermal and inhalation exposures are based on the most sensitive developmental effects of 

concern.

3.4.1 Completeness of the Toxicology Database

The toxicology data base is not complete for this non-food use chemical. There are three 

outstanding toxicological studies for paclobutrazol according to revised 40 CFR Part 158 

Toxicology Data Requirements. These studies include an acute neurotoxicity study, a 

subchronic neurotoxicity study, and an immunotoxicity study. The registrants have recently 

submitted the final ACN study report to the Agency. The Agency plans to review and 

incorporate the ACN into the revised Registration Review risk assessment. In addition, as 

specified in the 2012 HASPOC memo, the Agency will reevaluate the need for an SCN based on 
Paclobutrazol Human Health Risk Assessment DP No. D394230

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the results of the ACN. Consistent with current Agency policies, the need for an immunotoxicity 

study will also be reevaluated at that time.

An oral NOAEL is used for assessing inhalation risk for short and intermediate term exposure 

scenarios from occupational and residential uses. A repeated exposure inhalation study is not 

required at this time since the Margins of Exposure (MOEs) for all the occupational and 

residential inhalation exposure scenarios are greater than HED’s Level of Concern of 1000 

which includes the conventional 100 (10X for inter-species extrapolation and 10X for intraspecies variation) and a 10X for data gaps.

3.4.2 Evidence of Neurotoxicity

As discussed in Section 3.4.1, neither an acute nor a subchronic neurotoxicity study has been 

conducted for paclobutrazol. 

Paclobutrazol is a member of the triazole chemical class. Based on an initial review of the

experimental toxicology databases for triazole pesticides, at least seven triazoles resulted in 

evidence of neurotoxicity and have points of departure (PODs) based on acute, subchronic, or 

developmental neurotoxicity studies. Neurotoxic effects include reduced fore-limb grip strength, 

hyperactivity, clinical signs (piloerection, diarrhea, tip toe gait, hunched posture), and changes in 

motor activity. Because the triazoles as a chemical class appear to be neurotoxic, and there is not 

sufficient information to remove the requirements for these studies, the HASPOC concluded that 

the acute and subchronic neurotoxicity studies are required for paclobutrazol in accordance with 

revised 40 CFR Part 158 Toxicology Data Requirements (D. Smegal, TXR0056149, 01/03/12). 

The registrants have recently submitted the final ACN study report to the Agency. The Agency 

plans to review and incorporate the ACN into the revised Registration Review risk assessment. 

In addition, as specified in the 2012 HASPOC memo, the Agency will reevaluate the need for an 

SCN based on the results of the ACN. Consistent with current Agency policies, the need for an 

immunotoxicity study will also be reevaluated at that time.

3.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal

No evidence of increased quantitative or qualitative susceptibility was observed in 

developmental toxicity studies in rabbits or in a two-generation reproduction toxicity study in 

rats. However, increased quantitative susceptibility was seen in two developmental toxicity 

studies in rats. Developmental effects, in the form of delayed ossification and cleft palates, were 

seen at a maternally toxic dose in rats in one study while renal dilation, hydroureter and minor 

skeletal defects were seen in a second rat developmental study at doses lower than the highest 

dose tested, which was not toxic to the dams. 

The concern is low for the increased susceptibility seen in the rats since: 1) clear NOAELs and 

LOAELs were established for the developmental effects seen in two studies conducted in this 

species, 2) there was no evidence of increased susceptibility in two studies with rabbits; 3) there 

was no evidence of increased susceptibility in the offspring following exposures for two 

generations in the reproduction study, and 4) the developmental endpoints are used for assessing 

risk from dermal and inhalation exposures. Thus, there are no residual uncertainties for pre-and 

or post natal susceptibility.
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3.4.4 Residual Uncertainty in the Exposure Database

There are no residual uncertainties with regard to dietary (drinking water only) and residential 

exposure. Conservative, upper-bound assumptions were used to determine exposure through 

drinking water and residential sources, such that these exposures have not been underestimated.

3.5 Toxicity Endpoint and Point of Departure Selections

3.5.1 Dose-Response Assessment

The details for selecting toxicity endpoints and points of departure (PODs) are presented in 

Appendix A2. Based on the existing use pattern for paclobutrazol, the expected exposure profile 

will be for dietary (drinking water only), dermal, inhalation, and incidental oral exposures. 

Acute Dietary: No appropriate endpoints were identified from the available paclobutrazol 

toxicity studies for the acute dietary (drinking water only) scenario.

Chronic Dietary: Quantification of chronic dietary (drinking water only) risks was performed 

using the 2-year chronic/carcinogenicity feeding study in rats with a NOAEL of 10.8 mg/kg/day 

based on increased liver weights (both sexes), hypertrophy, and steatosis (both sexes) and 

decreased triglycerides (females) (LOAEL = 54.2 mg/kg/day). An Uncertainty Factor (UF) of 

1000 was applied to account for interspecies extrapolation (10X), intraspecies variability (10X), 

and the database uncertainty factor for lack of a neurotoxicity battery. The chronic reference 

dose (cRfD) was calculated to be 0.01 mg/kg/day.

Short-term Dermal: Quantification of dermal risks was performed using a developmental rat 

study with a NOAEL of 10 mg/kg/day based on renal dilation, hydroureter and minor skeletal 

defects or variations (LOAEL = 40 mg/kg/day). Since an oral dose was selected, a dermal 

absorption factor of 24.5% should be used in estimating dermal risks (see Section 3.2.1). An

MOE of 1000 is required which includes interspecies extrapolation (10X), intraspecies 

variability (10X), and the database uncertainty factor for lack of a neurotoxicity battery.

Short-term Inhalation: Quantification of inhalation risks was performed using a developmental 

rat study with a NOAEL of 10 mg/kg/day based on renal dilation, hydroureter and minor skeletal 

defects or variations (LOAEL = 40 mg/kg/day). Since an oral dose was selected absorption via 

inhalation is presumed to be equivalent to oral absorption. An MOE of 1000 is required which 

includes for interspecies extrapolation (10X), intraspecies variability (10X), and the database 

uncertainty factor for lack of a neurotoxicity battery.

Short-term Incidental Oral: Quantification of incidental oral ingestion risks was performed using 

a 90-day oral rat study with a NOAEL of 18.8 mg/kg/day based on elevated liver weights, and 

changes in clinical chemistry parameters associated with the liver (LOAEL = 93 mg/kg/day). An

MOE of 1000 is required which includes interspecies extrapolation (10X), intraspecies 

variability (10X), and the database uncertainty factor for lack of a neurotoxicity battery.
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3.5.2 Recommendation for Combining Routes of Exposure for Risk Assessment

When there are potential occupational and residential exposures to a pesticide, the risk 

assessment must address exposures from three major sources: oral, dermal and inhalation 

exposures, and determine whether the individual exposures can be combined if they have the 

same toxicological effects. For paclobutrazol, dermal and inhalation exposures can be combined 

since developmental toxicity from an oral study was selected for the dermal and inhalation 

routes. 

3.5.3 Cancer Classification and Risk Assessment Recommendations

There are no currently registered food uses for paclobutrazol. Carcinogenicity studies are not 

required for non-food use chemicals. Carcinogenicity studies in mice and rats are available for 

paclobutrazol and these studies were reviewed in 1994 by the RfD Peer Committee (TXR 

0011081). At that time the Agency was unable to determine the potential carcinogenicity of 

paclobutrazol because the maximum tolerated dose (MTD) was not achieved in the 2-year 

carcinogenicity/chronic study in rats and the carcinogenicity/chronic study in mice. The 

carcinogenic potential will be re-evaluated if the use pattern changes (i.e., food uses are 

proposed).
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3.5.4 Points of Departure and Toxicity Endpoints Used in Human Risk Assessment

Table 3.5.4a: Summary of Toxicological Doses and Endpoints for Paclobutrazol for Use in Dietary and 

Non-Occupational Human Health Risk Assessments

Exposure/

Scenario

Point of 

Departure

Uncertainty 

Factors

Level of Concern for 

Risk Assessment Study and Toxicological Effects

Acute Dietary No appropriate endpoints were identified from the available paclobutrazol toxicity studies for the acute dietary

(drinking water only) scenario.

Chronic Dietary

NOAEL = 

10.8 mg/kg/day

UFA=10x

UFH=10x

UFDB =10x

10.8mg/kg/day NOAEL 

 1000 (UF)

cRfD = 0.11 mg/kg/day 

Chronic (2-Year Rat) Feeding Toxicity MRID 

40734301

LOAEL = 54.2 mg/kg/day 2, based on increased 

liver weights (both sexes), hypertrophy, and 

steatosis (both sexes) and decreased 

triglycerides (females)

Incidental Oral 

Short- and IntermediateTerm

NOAEL = 

18.8 mg/kg/day

UFA=10x

UFH=10x

UFDB =10x

Residential LOC = 1000

90-Day Oral Toxicity Study in Rats

MRID 00132689

LOAEL = 93 mg/kg/day, based on elevated 

liver weights and changes in clinical chemistry 

parameters associated with the liver

Dermal

Short- and IntermediateTerm

Oral NOAEL = 10 

mg/kg/day

(Dermal 

Absorption rate = 

24.5%)

UFA=10x

UFH=10x

UFDB =10x

Residential LOC = 1000

Developmental (Rat) Toxicity Study 

MRID 00143158 

LOAEL = 40 mg/kg/day, based on renal 

dilation, hydroureter, and minor skeletal defects 

or variations

Inhalation Short- and 

Intermediate-Term

Oral NOAEL = 10 

mg/kg/day

UFA=10x

UFH=10x

UFDB =10x

Residential LOC = 1000

Developmental (Rat) Toxicity Study 

MRID 00143158 

LOAEL for this study is 40 mg/kg/day, based 

on renal dilation, hydroureter, and minor 

skeletal defects or variations

Cancer (oral, dermal, 

inhalation) Not required for non-food use pesticides.

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). UFDB = database uncertainty factor. MOE = margin of exposure. LOC = level of concern. N/A = not 

applicable.

Table 3.5.4b: Summary of Toxicological Doses and Endpoints for Paclobutrazol for Use in Dietary and 

Non-Occupational Human Health Risk Assessments

Exposure/

Scenario Point of Departure Uncertainty Factors

Level of Concern for Risk 

Assessment Study and Toxicological Effects

Dermal

Short- and 

Intermediate-Term

Oral NOAEL = 10 

mg/kg/day

(Dermal Absorption 

rate = 24.5%)

UFA=10x

UFH=10x

UFDB =10x

Occupational LOC = 1000

Developmental (Rat) Toxicity Study 

MRID 00143158 

LOAEL = 40 mg/kg/day, based on renal 

dilation, hydroureter, and minor skeletal 

defects or variations

Inhalation Short- and 

Intermediate-Term

Oral NOAEL = 10 

mg/kg/day

UFA=10x

UFH=10x

UFDB =10x

Occupational LOC = 1000

Developmental (Rat) Toxicity Study 

MRID 00143158 

LOAEL for this study is 40 mg/kg/day, 

based on renal dilation, hydroureter, and 

minor skeletal defects or variations

Cancer (oral, dermal, 

inhalation) Not required for non-food use pesticides.

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). UFDB = database uncertainty factor. MOE = margin of exposure. LOC = level of concern. N/A = not 

applicable.
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3.6 Endocrine Disruption

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse 

outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and 

chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, 

reproductive, and general or systemic toxicity. These studies include endpoints which may be 

susceptible to endocrine influence, including effects on endocrine target organ histopathology, 

organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, 

and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and 

chronic studies that assess growth, developmental and reproductive effects in different 

taxonomic groups. As part of registration review, EPA will review these data and select the most 

sensitive endpoints for relevant risk assessment scenarios from the existing hazard database. 

However, as required by FFDCA section 408(p), paclobutrazol is subject to the endocrine 

screening part of the Endocrine Disruptor Screening Program (EDSP).

EPA has developed the EDSP to determine whether certain substances (including pesticide 

active and other ingredients) may have an effect in humans or wildlife similar to an effect 

produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator 

may designate.” The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine-related effects caused by the substance, and 

establish a dose-response relationship between the dose and the E, A, or T effect. 

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between 

October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 

chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. In November 

of 2010, issued test orders/data call-ins for the second group of 134 chemicals, which contains 51

pesticide active ingredients. Paclobutrazol is among the group of 51 pesticide active ingredients 

on the second list to be screened under the EDSP. Accordingly, as part of registration review, 

EPA will issue future EDSP orders/data call-ins, requiring the submission of EDSP screening 

assays for paclobutrazol. For further information on the status of the EDSP, the policies and 

procedures, the list of chemicals, future lists, the test guidelines and the Tier 1 screening battery, 

please visit our website: http://www.epa.gov/endo/.

4.0 Dietary Exposure and Risk Assessment

4.1 Summary of Environmental Degradation

Tier I Drinking Water Assessment for the Registration Review of Paclobutrazol, D395022, F. Khan, 

01/05/12

Available data suggest that paclobutrazol is stable to hydrolysis and photolysis. Under aerobic 

conditions, paclobutrazol appears to be generally quite persistent in acidic soils, with half-lives 

greater than 300 days. However in soils with neutral or higher pH, estimated half-lives were as 
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short as 25 days. In anaerobic aquatic metabolism studies, paclobutrazol variably partitioned to 

the sediment and degraded with a half-life of more than one year in flood loam and silt loam 

soils. Since, the extrapolated half-lives were beyond the duration of experiment, paclobutrazol 

was considered stable in the anaerobic aquatic system. Paclobutrazol residues were persistent 

and mobile in terrestrial field dissipation studies. Paclobutrazol residues ranged from 450-950 

days for orchard soils (CA, WV, and FL) and 175-252 days in agricultural soils (MS, NC, and 

IL). Two major environmental degradates, ketone analog of parent (CGA 149907, ≤ 40.0%) and 

1H-1,2,4-triazol-3-ol (NOA457654, ≤ 25.1%) were identified in the environmental fate and 

terrestrial field dissipation studies.

4.2 Food Residue Profile

There are no currently registered food uses for paclobutrazol.

4.3 Water Residue Profile

There are no monitoring data currently available for paclobutrazol or its residues of concern in 

drinking water. Estimated drinking water concentrations (EDWCs) were generated using 

computer modeling methods. The screening model FIRST (FQPA Index Reservoir Screening 

Tool, version 1.1, 01/01/07) was used to calculate the surface water EDWCs. Estimated 

groundwater EDWCs were calculated using the screening model SCI-GROW (Screening 

Concentrations in Ground Water, version 2.3, 07/29/03).

The surface water and groundwater modeling were conducted with the highest application rate 

scenario which is 6.1 lbs/A for nursery production of container-grown ornamentals through soil 

drench method. This rate was normalized with the lowest fraction (0.59) of paclobutrazol 

retained in the soil column leaching study which resulted in an effective modeled drinking water 

application rate of 2.5 lbs/A. The maximum surface and ground water EDWCs for use in the 

human health risk assessment for paclobutrazol are shown in Table 4.3.

 

Table 4.3: Maximum Estimated Surface Water and Groundwater Concentrations for 

Paclobutrazol

Drinking Water Source Model Use rate

(lbs ai/A/season)

Acute

(μg/L)

Chronic

(μg/L)

Parent only

Surface water FIRST

2.501

133.5 43.52

Groundwater SCI-GROW 20.0 20.0

1 Maximum rate of 6.1 lbs/A was normalized with the lowest fraction (0.59) of paclobutrazol retained in the soil 

column leaching study.

2 Bolded value was used for the chronic dietary assessment.
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4.4 Dietary Risk Assessment

Although there are no registered food uses for paclobutrazol, dietary exposure is possible via 

drinking water. In accordance with typical HED dietary exposure assessments which incorporate 

potential residues in drinking water, the modeled drinking water residues were incorporated into 

DEEM-FCID in the categories “water, direct, all sources” and “water, indirect, all sources.” 

4.4.1 Acute Dietary Risk Assessment

An acute dietary (drinking water only) exposure assessment was not performed as no appropriate 

endpoints were identified from the available paclobutrazol toxicity studies for the acute dietary 

scenario. 

4.4.2 Chronic Dietary Risk Assessment

A chronic dietary (drinking water only) exposure assessment was performed that directly 

incorporated potential drinking water residues. The estimated exposure (drinking water only) to 

the highest population subgroup (all infants < 1 year old) resulted in an estimated risk equivalent 

to 27% of the chronic reference dose (cRfD). The estimated exposure (drinking water only) to 

the general U.S. population resulted in an estimated risk equivalent to 8% of the chronic 

reference dose (cRfD). 

4.4.3 Cancer Dietary Risk Assessment

There are no currently registered food uses for paclobutrazol. Carcinogenicity studies are not 

required for non-food use chemicals. Carcinogenicity studies in mice and rats are available for 

paclobutrazol and these studies were reviewed in 1994 by the RfD Peer Committee (TXR 

0011081). At that time the Agency was unable to determine the potential carcinogenicity of 

paclobutrazol because the maximum tolerated dose (MTD) was not achieved in the 2-year 

carcinogenicity/chronic study in rats and the carcinogenicity/chronic study in mice. The 

carcinogenic potential and the need for a cancer dietary assessment will be re-evaluated if the use 

pattern changes (i.e., food uses are proposed).
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4.4.4 Dietary Risk Assessment Summary Table

Table 4.4.4: Summary of Dietary (Drinking Water Only)

Exposure and Risk Estimates for Paclobutrazol

Population Subgroup

Chronic Dietary

Dietary Exposure

(mg/kg/day) % cPAD

General U.S. Population 0.000917 8

All Infants (< 1 year old) 0.003006 27

Children 1-2 years old 0.001362 12

Children 3-5 years old 0.001275 12

Children 6-12 years old 0.000879 8

Youth 13-19 years old 0.000663 6

Adults 20-49 years old 0.000856 8

Adults 50+ years old 0.000901 8

Females 13-49 years old 0.000853 8

5.0 Residential (Non-Occupational) Exposure/Risk Characterization

Paclobutrazol is currently registered for use as a foliar spray for turf (including parks, athletic 

fields, residential lawns, and golf courses). Although, paclobutrazol products do not appear to be 

specifically marketed towards residential handler use (i.e., homeowners); a residential handler 

assessment was performed to be protective of any such use. A residential postapplication 

assessment was also performed as use of paclobutrazol in parks, residential lawns, and golf 

courses is expected to result in residential postapplication exposure. In assessing these 

exposures, the Health Effects Division’s 2012 Standard Operating Procedures for Residential 

Pesticide Exposure Assessment: Lawns/Turf was used. Some of the data included in the 

Lawns/Turf SOP are proprietary and thus are subject to the data protection provisions of the 

Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA).

5.1 Residential Handler Exposure and Risk

Residential handler exposures may occur via the dermal and inhalation routes while a 

homeowner is using paclobutrazol to treat a residential lawn. As a result, a dermal and 

inhalation residential handler exposure assessment was performed for paclobutrazol. The 

duration of handler exposure relevant to the proposed use pattern is short-term. Dermal and 

inhalation handler risks were assessed only for adults. Based on the existing use pattern, HED 

expects the following residential pesticide handler scenarios:

1) mixing/loading/applying liquids with a backpack sprayer;

2) mixing/loading/applying liquids with a manually pressurized sprayer;

3) mixing/loading/applying liquids with a hose-end sprayer;
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4) loading/applying granulars via a push-type spreader; and 

5) loading/applying granulars via a belly grinder.

It is the policy of HED to use the best available data to assess handler exposure. Sources of 

generic handler data, used as surrogate data in the absence of chemical-specific data, include the 

Pesticide Handlers Exposure Database Version 1.1 (PHED 1.1), the Outdoor Residential 

Exposure Task Force (ORETF) database, or other registrant-submitted occupational exposure 

studies. Some of these data are proprietary (e.g., ORETF data), and subject to the data protection 

provisions of FIFRA. The standard values recommended for use in predicting residential handler 

exposure that are used in this assessment, known as “unit exposures”, are outlined in 2012 

Lawns/Turf SOP.

All residential handler dermal exposure scenarios do not exceed HED’s level of concern (MOEs 

≥ 1000) except for the belly grinder scenario (MOE = 790). Handler exposure and risk estimates 

are summarized in Table 5.1.1.

Table 5.1.1: Residential Handler Exposure and Risk Estimates for Paclobutrazol

Scenario

Application 

Rate a

(lb ai/A)

Area 

Treated 

Daily b

(acres/day)

Dermal 

Unit 

Exposure b 

(mg/lb ai)

Inhalation 

Unit 

Exposure b 

(mg/lb ai)

Dermal 

Dosec

(mg/kg/day)

Dermal 

MOEd

Inhalation 

Dosee

(mg/kg/day)

Inhalation 

MOEf

Total

Dermal +

Inhalation 

MOE

Mixer/Loader/Applicator 

(Liquids) - Manually 

Pressurized Handwand 

Application

Turf

0.75

0.023 g63 0.018 0.0033 3000 0.0000039 2600000 3000

Mixer/Loader/Applicator 

(Liquids) - Hose End 

Sprayer Application

0.5 13.4 0.022 0.024 2500 0.000048 1200000 2500

Mixer/Loader/Applicator 

(Liquids) - Backpack 

Sprayer Application

0.023 g130 0.14 0.0069 1500 0.00003 330000 1400

Mixer/Loader/Applicator 

(Granules) - Push Type 

Spreader Application 0.5

0.5 0.81 0.0026 0.00062 16000 0.0000081 1200000 16000

Mixer/Loader/Applicator 

(Granules) - Belly 

Grinder Application

0.023 g360 0.039 0.013 790 0.0000056 1800000 790

a. Application rates = maximum application rates from labels.

b. Data taken from 2012 Lawns/Turf SOP.

c. Dermal Dose = exposure (mg/lb ai) x App Rate x Area Treated x %Abs (24.5% dermal ) / Body weight (80 kg). 

d. Dermal MOE = NOAEL (10 mg/kg/day)/Dermal Dose.

e. Inhalation Dose = Unit exposure (mg/lb ai) x App Rate x Area Treated x %Abs (100% inhalation ) / Body weight (80 kg). 

f. Inhalation MOE = NOAEL (10 mg/kg/day) / Inhalation Dose (mg/kg/day)

g. 0.023 acres is equivalent to 1,000 ft2.

5.2 Residential Postapplication Exposure and Risk

Residential postapplication exposures may occur via the dermal and oral routes after a residential 

lawn is treated with paclobutrazol. Residential postapplication exposures may also occur via the 

dermal route after a golf course is treated with paclobutrazol. As a result, a dermal residential 

postapplication exposure assessment was performed for paclobutrazol. Based on the existing use 

pattern, HED expects the following residential postapplication scenarios:
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1) dermal postapplication exposure for adults playing on treated turf;

2) dermal and oral postapplication exposure for children 1<2 years olds playing on treated 

turf; 

3) dermal postapplication exposure for adults and children 11 < 16 years old mowing treated 

turf; and

4) dermal postapplication exposure for adults, children 11 < 16 years old, and children 6 < 11 

years old playing golf on treated turf.

The lifestages (i.e., adults, children 1<2 years old, children 11 < 16 years old, and children 6 < 11 

years old) selected for each postapplication scenario are based on an analysis provided as an 

Appendix in the 2012 Residential SOPs. These lifestages are not the only lifestages that could be 

potentially exposed for these postapplication scenarios; however, the assessment of these lifestages is 

health protective for the exposures and risks for any other potentially exposed lifestages.

Dermal and oral exposures during postapplication activities were estimated using exposure 

algorithms and other standard assumptions (e.g., transfer coefficients, exposure time, fraction of 

pesticide on hands, hand-to-mouth events) taken from the 2012 Lawns/Turf SOP. A TTR study 

was also used to assess the liquid formulation scenarios (Turf Enhancer® 2SC Plant Growth 

Regulator Transferable Turf Residue Study – MRID No.: 45214201). Data were collected at 

three sites in the TTR study including New York, California, and North Carolina. Data from the 

California site was used in this assessment as it resulted in the highest predicted Day 0 residues.

5.2.1 Dermal Postapplication Exposure

All adult and children mowing and golf dermal risk estimates for both liquid and granular 

formulations do not exceed HED’s level of concern (MOEs ≥ 1000). All adult and children 

playing on treated turf dermal risk estimates for both liquid and granular formulations exceed 

HED’s level of concern (MOEs ≥ 1000). A summary of the adult and children short-term dermal

exposure and risk estimates is shown in Table 5.2.1.
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Table 5.2.1: Short-Term Dermal Residential Post-application Exposure and Risk 

Estimates for Paclobutrazol

Lifestage Post-application Exposure Scenario Application Rate a

(lb ai/A)

TTR 

(ug/cm2)

Dermal Dose b

(mg/kg/day)

Dermal 

MOEs c

Liquid Formulations

Adult

Dermal 

Physical Activities on Turf

0.75 0.077 d

0.064 160

Mowing 0.0013 7700

Golfing 0.005 2000

Child 11 < 16 years old Mowing 0.0015 6700

Golfing 0.0058 1700

Child 6 < 11 years old Golfing 0.0069 1500

Child 1 < 2 year old Physical Activities on Turf 0.12 82

Granular Formulations

Adult

Dermal 

Physical Activities on Turf

0.5 0.011 e

0.010 970

Mowing 0.00019 53000

Golfing 0.00073 14000

Child 11 < 16 years old Mowing 0.00022 46000

Golfing 0.00084 12000

Child 6 < 11 years old Golfing 0.00099 10000

Child 1 < 2 year old Physical Activities on Turf 0.019 520

a. Application rates = maximum application rates from labels.

b. Dermal Dose (mg/kg/day) = TTR (μg/cm2) x 0.001 (mg/μg) x short-term TC (cm2/hr) x ET (hr/day) x DAF (40%)

BW (kg) 

c. Dermal MOE = NOAEL (10 mg/kg/day) / Dermal Dose (mg/kg/day)

d. Representative of California TTR data taken from MRID No.: 45214201; the site that resulted in the highest TTR values.

e. Turf Transferable Residues (TTR) = Application Rate x 0.2% x 11.2

5.2.2 Oral Postapplication Exposure

All children oral non-dietary ingestion risk estimates for both liquid and granular formulations

do not exceed HED’s level of concern (MOEs ≥ 1000). A summary of the children short-term 

oral non-dietary ingestion exposure and risk estimates is shown in Table 5.2.2.

Table 5.2.2: Short-Term Oral Non-dietary Ingestion Residential Post-application 

Exposure and Risk Estimates for Paclobutrazol

Lifestage Post-application Exposure Scenario Application Rate a

(lb ai/A)

TTR 

(ug/cm2)

Oral Dose b, c, d

(mg/kg/day)

Oral 

MOEs e

Liquids

Child 1 < 2 year old Oral 

Hand-to-Mouth

0.75 0.077 f

0.010 1800

Object-to-Mouth 0.00032 59000

Soil Ingestion 0.000025 770000

Granulars

Child 1 < 2 year old Oral 

Hand-to-Mouth

0.5 0.011 g

0.00074 25000

Object-to-Mouth 0.00023 82000

Soil Ingestion 0.000016 1200000

Episodic Granular Ingestion N/A h

a. Application rates = maximum application rates from labels.

b. Hand-to-Mouth Dose (mg/kg/day) = E = [HR * (FM * SAH) * (ET * N_Replen) * (1- (1- SE)

(Freq_Replen/N-Replen))]

c. Object-to-Mouth Dose (mg/kg/day) = E = [OR* CF1 * SAMO * (ET * N_Replen) * (1- (1- SEO)

(Freq_Replen/N_Replen))]

d. Soil Ingestion Dose (mg/kg/day) = E = SRt * SIgR * CF1

e. Oral MOE = NOAEL (18.8 mg/kg/day) / Oral Dose (mg/kg/day)

f. Representative of California TTR data taken from MRID No.: 45214201; the site that resulted in the highest TTR values.

h. Turf Transferable Residues (TTR) = Application Rate x 0.2% x 11.2

g. No endpoints identified from the available developments toxicity studies (rat and rabbit) appropriate for an acute dietary 

assessment for paclobutrazol and thus no assessment is required for episodic granular ingestion.
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5.2.3 Inhalation Postapplication Exposure

Based on the Agency's current practices, a quantitative residential postapplication inhalation 

exposure assessment was not performed for paclobutrazol at this time primarily because 

paclobutrazol’s vapor pressure (1.28 x 10-9mm Hg @ 25.0°C) and Henry's Law Constant (8.09 x 

10-10 atm m3/mol) indicate that the compound is relatively non-volatile under field conditions. 

However, volatilization of pesticides may be a potential source of postapplication inhalation 

exposure to individuals nearby pesticide applications. The Agency sought expert advice and 

input on issues related to volatilization of pesticides from its Federal Insecticide, Fungicide, and 

Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s 

final report on March 2, 2010 

(http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The Agency is in the 

process of evaluating the SAP report and may, as appropriate, develop policies and procedures to 

identify the need for and, subsequently, the way to incorporate postapplication inhalation 

exposure into the Agency's risk assessments. If new policies or procedures are put into place, the 

Agency may revisit the need for a quantitative postapplication inhalation exposure assessment 

for paclobutrazol.

5.3 Combined Residential Risk Estimates

HED combines risk values resulting from separate exposure pathways when it is likely they can 

occur simultaneously based on the use pattern, the behavior associated with the exposed 

population, and the hazard associated with the points of departure. HED reviewed all residential 

sources of exposure to determine which residential exposure scenarios would be appropriate to 

combine with dietary exposure for an aggregate risk assessment. 

HED did not combine exposure resulting from adult handler and postapplication exposure 

resulting from treated lawns and/or golfing because of the conservative assumptions and inputs 

within each estimated exposure scenario. HED believes that combing exposures resulting from 

handler and postapplication activities would result in an overestimate of adult exposure. 

Therefore, HED selected the most conservative adult residential scenario, dermal postapplication 

exposure (MOE = 160) as the contributing source of residential exposure to be combined with 

the dietary exposure for the aggregate assessment.

The children’s oral exposure is based on postapplication hand-to-mouth exposures only. To 

include exposure from object-to-mouth and soil ingestion in addition to hand-to-mouth could 

result in a very conservative estimation of exposure, as it would overestimate the potential for

oral exposure. Furthermore, although there is the potential for co-occurrence of dermal and oral 

exposure, the toxicological effects from the dermal and oral routes of exposure are different. As 

a result, a combined residential exposure assessment is not possible for children. Therefore, two 

independent children’s aggregate assessments are required (postapplication dermal combined 

with dietary exposure and postapplication oral combined with dietary exposure) to ensure no 

unacceptable risk will result to children when combining residential and dietary exposure for 

purposes of estimating an aggregate risk.
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Table 5.3 summarizes the residential exposure scenarios that are to be used for estimating 

aggregate exposure. 

Table 5.3. Combined Residential Exposure and Risk Estimates for Paclobutrazol

Use Site

Handler 

Dermal a

Handler

Inhalation a

Post-application 

Dermal MOE b

Hand-to-Mouth 

MOE c

Dose MOE Dose MOE Dose MOE Dose MOE

Adults – Turf (Granulars) 0.013 790 0.0000056 1800000 0.010 970 N/A

Adults – Turf (Liquids) 0.0069 1500 0.00003 330000 0.064 160 N/A

Children 1 < 2 Years Old 

- Turf (Granulars) N/A N/A 0.019 520 0.00074 25000

Children 1 < 2 Years Old 

- Turf (Liquids) N/A N/A 0.12 82 0.010 1800

a. See Table 5.1.1: Residential Handler Dermal Exposure and Risk (granulars represents belly grinder and liquids represents 

backpack sprayer)

b. See Table 5.2.1 Dermal Postapplication Exposure and Risk

c. See Table 5.2.2 Hand-To-Mouth Exposure and Risk

5.4 Spray Drift

Off-target movement of pesticides can occur via many types of pathways and it is governed by a 

variety of factors. Sprays that are released and do not deposit in the application area end up offtarget and can lead to exposures to those it may directly contact. They can also deposit on 

surfaces where contact with residues can eventually lead to indirect exposures (e.g., children 

playing on lawns where residues have deposited next to treated fields). The potential risk 

estimates from these residues can be calculated using drift modeling coupled with methods 

employed for residential risk assessments for turf products.

The approach to be used for quantitatively incorporating spray drift into risk assessment is based 

on a premise of compliant applications which, by definition, should not result in direct exposures 

to individuals because of existing label language and other regulatory requirements intended to 

prevent them.1 Direct exposures would include inhalation of the spray plume or being sprayed 

directly. Rather, the exposures addressed here are thought to occur indirectly through contact 

with impacted areas, such as residential lawns, when compliant applications are conducted. 

Given this premise, exposures for children (1 to 2 years old) and adults who have contact with 

turf where residues are assumed to have deposited via spray drift thus resulting in an indirect 

exposure are the focus of this analysis analogous to how exposures to turf products are 

considered in risk assessment.

Paclobutrazol is not registered on use sites that are likely to result in spray drift outside of the 

currently registered turf uses. Since postapplication exposure from the direct turf applications is 

already assessed for paclobutrazol (see above in Section 5.2), quantitative assessment of spray 

drift is not required for paclobutrazol at this time.

 

1

This approach is consistent with the requirements of the EPA’s Worker Protection Standard which, 

when included on all labels, precludes direct exposure pathways.
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6.0 Aggregate Exposure/Risk Characterization

In accordance with the FQPA, HED must consider and aggregate (add) pesticide exposures and 

risks from three major sources: food, drinking water, and residential exposures. In an aggregate 

assessment, exposures from relevant sources are added together and compared to quantitative 

estimates of hazard (e.g., a NOAEL or PAD), or the risks themselves can be aggregated. When 

aggregating exposures and risks from various sources, HED considers both the route and 

duration of exposure.

6.1 Acute Aggregate Risk

An acute dietary (drinking water only) exposure assessment was not performed as no appropriate 

endpoints were identified from the available paclobutrazol toxicity studies for the acute dietary 

scenario. 

6.2 Short- and Intermediate-Term Aggregate Risk

The short- and intermediate-term toxicological endpoints for paclobutrazol are the same for each 

route of exposure. Therefore, for residential exposure scenarios, only short-term exposures were 

assessed, and are considered to be protective of intermediate-term exposure and risk.

There are six aggregate risk scenarios that are of interest to HED: 1) adult dermal 

postapplication exposure to granular formulations; 2) adult dermal postapplication exposure to 

liquid formulations; 3) children’s postapplication dermal exposure to granular formulations; 4) 

children’s postapplication dermal exposure to liquid formulations; 5) children’s hand-to-mouth 

exposure to granular formulations; and 6) children’s hand-to-mouth exposure to liquid 

formulations. Exposure from these six scenarios is aggregated with chronic dietary exposure 

(drinking water only) which is considered to be background exposure.

For the adult short- and intermediate-term aggregate risk assessment, chronic dietary exposure is 

added directly to the adult dermal postapplication exposure estimates. The chronic dietary 

exposure estimate for the general U.S. population was used to determine the aggregate risk 

estimate.

For the children’s short- and intermediate-term aggregate risk assessments, chronic dietary 

exposure is added directly to the children’s postapplication dermal and oral exposure estimates. 

As the toxic effects are different for these two routes of exposure, separate calculations were 

performed. Hand to mouth and dermal exposures for children 1 < 2 years old were separately 

combined with the chronic dietary exposure for children 1 < 2 years old.

All of the adult and children 1 < 2 years old chronic dietary + dermal aggregate risk estimates 

exceed HED’s level of concern (MOEs ≤ 1000). All of the children 1 < 2 years old chronic 

dietary + hand-to-mouth aggregate risk estimates do not exceed HED’s level of concern (MOEs 

≥ 1000). The results of the adult and children’s aggregate risk determinations are presented in 

Table 6.2.
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Table 6.2: Short- and Intermediate-Term Aggregate Risk Calculations

Lifestage Residential 

Scenario

NOAEL 

(mg/kg/day) LOC1

Chronic 

Dietary Dose 

for Drinking 

Water Only 

(mg/kg/day)

Residential 

Postapplication 

Dermal 

Exposure2

(mg/kg/day)

Residential 

Postapplication 

Hand-to-Mouth 

Exposure3

(mg/kg/day)

Total 

Exposure4

(mg/kg/day)

Aggregate 

MOE (food, 

water, and 

residential)5

Adult Male

Dermal TurfGranular

10

1000

0.000917

0.01 N/A 0.0109 920

Dermal TurfLiquid 0.064 N/A 0.0649 150

Children

1 < 2 yrs old

Dermal TurfGranular

0.001362

0.019 N/A 0.0204 490

Dermal TurfLiquid 0.12 N/A 0.1214 82

Children

1 < 2 yrs old

HtM TurfGranular 18.8

N/A 0.00074 0.0021 9000

HtM TurfLiquid N/A 0.010 0.01136 1700

1 The level of concern is 1000 which accounts for interspecies extrapolation (10x), intraspecies variation (10x) and additional 

database uncertainty factor (10x).

2 Residential Exposure = Dermal exposure from treated turf (see Table 5.2.1). 

3 Residential Exposure = Hand-to-mouth exposure from treated turf (see Table 5.2.2). 

4 Total Exposure = Chronic Food & Water Exposure + Residential Exposure

5 Exposure]

6.3 Chronic Aggregate Risk

The chronic aggregate risk assessment is equivalent to the chronic dietary risk assessment

(discussed in Section 4.4.4) as there are no residential scenarios that result in long-term 

exposure. All of the chronic dietary risk estimates do not exceed HED’s level of concern. 

6.4 Cancer Aggregate Risk

Paclobutrazol currently has no registered food uses and carcinogenicity studies are not required 

for non-food use pesticides under the 40 CFR Part 158 Toxicology Data Requirements. The 

Agency has not classified the carcinogenic potential of paclobutrazol and thus a cancer aggregate

risk assessment was not conducted at this time.

6.5 Updated Aggregate Assessment of Free Triazole & its Conjugates

Paclobutrazol is a member of the class of compounds known as the triazoles (a.k.a. triazolederivative fungicides, T-D fungicides, conazoles). In 2006, HED issued aggregate human health 

risk assessments for T and the conjugated triazole metabolites (D322215, M. Doherty, et al., 

2/7/06). Those assessments addressed a back-log of triazole use requests that had been held by 

the Agency pending resolution of various toxicological and exposure concerns for the common 

triazole metabolites. The findings of that assessment were that risk estimates for all exposure 

scenarios were below HED’s level of concern. Since that time, a number of requests for new 

uses of triazole-derivative fungicides have been submitted to the Agency. As a result of these 

requests, new dietary exposure estimates have been made for T and combined residues of TA, 

TAA, and TP, and new aggregate exposure and risk estimates are necessary (T. Morton, 

D397592, 01/26/2012). Neither the toxicological information nor the non-dietary exposure 

estimates detailed in the 2006 memorandum have changed; thus, the only alterations to the 
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previous aggregate exposure and risk estimates are due to changes in the dietary exposure 

estimates. For complete hazard characterization and non-dietary exposure assessments for the 

common triazole metabolites, see the 2006 risk assessment.

The revised aggregate estimates are summarized below for short- and intermediate-term 

scenarios for T (Tables 6.5a and 6.5b, respectively). The conjugated triazole metabolites are 

formed in plants by the conjugation of 1,2,4-T to serine. The TA may then be further 

metabolized to form TAA and/or TP. Because of the nature of this process, HED has assumed 

that it occurs within the plant itself and not on leaf surfaces. Therefore, the residues are not 

available for dermal, hand-to-mouth, or object-to-mouth exposures and HED has not conducted a 

residential exposure assessment for the triazole conjugates. Residues of TA, TAA, and TP may 

occur in soil. 1,2,4-Triazole is more toxic than TA/TAA/TP and exposures to these via soil 

ingestion are unlikely to exceed those of 1,2,4-T. The assessment for soil ingestion of 1,2,4-T 

shows that risk estimates are below HED’s level of concern; therefore, risk estimates for soil 

ingestion of the conjugates will also be below HED’s level of concern.

Table 6.5a. Short-term Aggregate Exposure and Risk Estimates for 1,2,4-Triazole

Population Subgroup

Exposure Estimate, mg/kg/day1

Aggregate 

MOE2 Dietary

Dermal

(M/L/A)

Dermal 

(PostApplic.)Hand-toMouthObject-toMouthSoil 

Ingestion Aggregate

U.S. Population (total) 0.001409 0.00183 0.0051 N/A N/A N/A 0.008339 3600

All infants (< 1 year) 0.001923 N/A 0.0086 0.0041 0.0010 0.000019 0.015642 1900

Children 1-2 yrs 0.003723 N/A 0.0086 0.0041 0.0010 0.000019 0.017442 1700

Children 3-5 yrs 0.002994 N/A 0.0086 0.0041 0.0010 0.000019 0.016713 1800

Children 6-12 yrs 0.001891 N/A 0.0086 N/A N/A N/A 0.010491 2900

Youth 13-19 yrs 0.001266 0.00183 0.0051 N/A N/A N/A 0.008196 3700

Adults 20-49 yrs 0.001162 0.00183 0.0051 N/A N/A N/A 0.008092 3700

Adults 50+ yrs 0.001097 0.00183 0.0051 N/A N/A N/A 0.008027 3700

Females 13-49 yrs 0.001167 0.00183 0.0051 N/A N/A N/A 0.008097 3700

1 Exposure estimates for dermal, hand-to-mouth, object-to-mouth, and soil ingestion are from J. Arthur, DP 322240, 12/9/05.

2 Aggregate MOE = NOAEL (30 mg/kg/day) ÷ Aggregate Exposure Estimate (mg/kg/day). Level of Concern = 1000.

Table 6.5b. Intermediate-term Aggregate Exposure and Risk Estimates for 1,2,4-Triazole

Population Subgroup

Exposure Estimate, mg/kg/day

Aggregate MOE2 Dietary Soil Ingestion1 Aggregate

U.S. Population (total) 0.001409 N/A 0.001409 11000

All infants (< 1 year) 0.001923 0.000019 0.001942 7700

Children 1-2 yrs 0.003723 0.000019 0.003742 4000

Children 3-5 yrs 0.002994 0.000019 0.003013 5000

Children 6-12 yrs 0.001891 N/A 0.001891 7900

Youth 13-19 yrs 0.001266 N/A 0.001266 12000

Adults 20-49 yrs 0.001162 N/A 0.001162 13000

Adults 50+ yrs 0.001097 N/A 0.001097 14000

Females 13-49 yrs 0.001167 N/A 0.001167 13000

1 Soil ingestion estimates are from J. Arthur, DP 322240, 12/9/05

2 Aggregate MOE = NOAEL (15 mg/kg/day) ÷ Aggregate Exposure Estimate (mg/kg/day). Level of Concern = 3000.
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7.0 Cumulative Exposure/Risk Characterization

Unlike other pesticides for which EPA has followed a cumulative risk approach based on a 

common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as 

to paclobutrazol and any other substances. For the purposes of this assessment, therefore, EPA 

has not assumed that paclobutrazol has a common mechanism of toxicity with other substances. 

For information regarding EPA’s efforts to determine which chemicals have a common 

mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the policy 

statements released by EPA’s Office of Pesticide Programs concerning common mechanism 

determinations and procedures for cumulating effects from substances found to have a common 

mechanism on EPA’s website at http://www.epa.gov/pesticides/cumulative/.

8.0 Occupational Exposure/Risk Characterization

Paclobutrazol is currently registered for use as a foliar spray for turf (including parks, athletic 

fields, residential lawns, and golf courses); a foliar spray for ornamentals in greenhouses and 

nurseries; as a tree injection; as a tree root drench; and as a seed treatment. Based on the existing 

use pattern for paclobutrazol, there is potential for both occupational handler and occupational 

post-application exposure to occur.

8.1 Short- and Intermediate-Term Handler Risk

8.1.1 Short- and Intermediate-Term Handler Risk for Turf, Ornamental, and Tree Uses

Paclobutrazol is currently registered for use as a foliar spray for turf (including parks, athletic 

fields, residential lawns, and golf courses); a foliar spray for ornamentals in greenhouses and 

nurseries; and as a tree injection; as a tree root drench (see Table 2.3). Based on the existing use 

pattern, HED expects the following occupational pesticide handler scenarios:

5) mixing/loading liquids for ground applications;

6) mixing/loading liquids for tree injections;

7) mixing/loading liquids for dips;

8) mixing/loading wettable powders for tree injections;

9) mixing/loading granulars for ground applications;

10) applying sprays via groundboom equipment; 

11) applying granulars via tractor drawn spreader;

12) mixing/loading/applying liquids with a backpack sprayer;

13) mixing/loading/applying liquids with a manually pressurized sprayer;

14) mixing/loading/applying liquids with a mechanically pressurized sprayer; and

15) loading/applying granulars via a push-type spreader.

It is the policy of HED to use the best available data to assess handler exposure. Sources of 

generic occupational handler data, used as surrogate data in the absence of chemical-specific 

data, include the Pesticide Handlers Exposure Database Version 1.1 (PHED 1.1), the 

Agricultural Handler Exposure Task Force (AHETF) database, the Outdoor Residential 

Exposure Task Force (ORETF) database, or other registrant-submitted occupational exposure 
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studies. Some of these data are proprietary (e.g., AHETF data) and subject to the data protection 

provisions of FIFRA. The standard values recommended for use in predicting occupational 

handler exposure that are used in this assessment, known as “unit exposures”, are outlined in the 

“Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” 

(http://www.epa.gov/opp00001/science/handler-exposure-table.pdf), which, along with 

additional information on HED policy on use of surrogate data, including descriptions of the 

various sources, can be found at http://www.epa.gov/pesticides/science/handler-exposuredata.html.

Handler exposure is expected to be short- or intermediate-term in duration based on information 

provided on the proposed labels. In addition, the short- and intermediate-term toxicological 

endpoints are the same for the respective routes of exposure; therefore, the estimates of risk for 

short-term duration exposures are protective of those for intermediate-term durations. Long-term 

exposures are not expected; therefore, a long-term assessment was not conducted. 

Table 8.1.1 presents the estimated dermal and inhalation risk estimates from the paclobutrazol 

turf, ornamental, and tree uses for occupational handlers. The short- and intermediate-term risk 

estimates for most occupational handler scenarios do not exceed HED’s level of concern (MOEs 

> 1000) at some level of personal protective equipment (PPE). However, there are some 

handheld equipment scenarios that exceed HED’s level of concern (MOEs < 1000) even with the 

use of PPE.
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Table 8.1.1. Occupational Handler Exposures and Risks for Paclobutrazol Turf, Ornamental, and Tree Uses

Activity Use Site

PPE-G 

Dermal 

Unit 

Exposure 

(mg/lb ai)a

PPE-DL 

Dermal 

Unit 

Exposure 

(mg/lb ai)a

Baseline 

Inhalation 

Unit 

Exposure 

(mg/lb ai)a

Application 

Rate b

Area 

Treated 

Daily c

PPE-G PPE-G, DL Baseline Inhalation Total MOE 

(PPE-G + 

Baseline 

Inhalation)

Total MOE 

(PPE G-DL 

+ Baseline 

Inhalation)

Dermal 

Dose 

(mg/kg/day)d

MOEf

Dermal 

Dose 

(mg/kg/day)d

MOEf Dose 

(mg/kg/day)e MOEg

Mixing/Loading Liquids

Groundboom 

Applications on 

Ornamentals in 

Nurseries

0.0376 0.0291 0.000219

0.59 lb ai/A 40 A 0.0027 3,700 0.0021 4,800 0.000065 150,000 3,600 4,600

Groundboom 

Applications on Golf 

Courses

0.75 lb ai/A 40 A 0.0035 2,900 0.0027 3,700 0.000082 120,000 2,800 3,600

Tree Injection (8 

diameter Inch Trees)

0.0099 lb 

ai/tree 50 trees 0.000057 180,000 0.000044 230,000 0.0000014 7,400,000 170,000 220,000

Tree Injection (35 

diameter Inch Trees) 0.07 lb ai/tree 50 trees 0.0004 25,000 0.00031 32,000 0.0000096 1,000,000 24,000 31,000

Tree Soil Injection 0.352 lb 

ai/tree 50 trees 0.002 4,900 0.0016 6,400 0.000048 210,000 4,800 6,200

Dips for Plug/Liner 

Soaks

0.000051 lb 

ai/gal 100 gals 0.00000059 17,000,000 0.00000045 22,000,000 1.40E-08 720,000,000 17,000,000 21,000,000

0.000051 lb 

ai/gal 1000 gals 0.0000059 1,700,000 0.0000045 2,200,000 1.40E-07 72,000,000 1,700,000 2,100,000

Dips for Bulb Soaks 

(Freesia)

0.00255 lb 

ai/gal 100 gals 0.000029 340,000 0.000023 440,000 0.0000007 14,000,000 330,000 430,000

0.00255 lb 

ai/gal 1000 gals 0.00029 34,000 0.00023 44,000 0.000007 1,400,000 33,000 43,000

Mixing/Loading Wettable 

Powders

Tree Injection (6-16 

inches in diameter)

0.17 0.13 0.043

0.000059 lb 

ai/tree 50 trees 0.0000015 6,500,000 0.0000012 8,500,000 0.0000016 6,300,000 3,200,000 3,600,000

Tree Injection (>16 

inches in diameter)

0.00024 lb 

ai/tree 50 trees 0.0000062 1,600,000 0.0000048 2,100,000 0.0000065 1,600,000 790,000 890,000

Loading Granulars

Tractor Drawn 

Spreader 

Applications on Golf 

Courses

0.0069 0.0034 0.0017 0.5 lb ai/A 40 A 0.00042 24,000 0.00021 48,000 0.00043 24,000 12,000 16,000

Applying Liquid Sprays 

via Grounboom

Golf Courses

0.0161 0.0126 0.00034

0.75 lb ai/A 40 A 0.0015 6,800 0.0012 8,600 0.00013 78,000 6,200 7,800

Ornamentals in 

Nurseries 0.59 lb ai/A 40 A 0.0012 8,600 0.00091 11,000 0.0001 100,000 7,900 9,900

Applying Granulars via 

Tractor Drawn Spreader Golf Courses 0.0072 0.0042 0.0012 0.5 lb ai/A 40 A 0.00044 23,000 0.00026 39,000 0.0003 33,000 13,000 18,000
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Table 8.1.1. Occupational Handler Exposures and Risks for Paclobutrazol Turf, Ornamental, and Tree Uses

Activity Use Site

PPE-G 

Dermal 

Unit 

Exposure 

(mg/lb ai)a

PPE-DL 

Dermal 

Unit 

Exposure 

(mg/lb ai)a

Baseline 

Inhalation 

Unit 

Exposure 

(mg/lb ai)a

Application 

Rate b

Area 

Treated 

Daily c

PPE-G PPE-G, DL Baseline Inhalation Total MOE 

(PPE-G + 

Baseline 

Inhalation)

Total MOE 

(PPE G-DL 

+ Baseline 

Inhalation)

Dermal 

Dose 

(mg/kg/day)d

MOEf

Dermal 

Dose 

(mg/kg/day)d

MOEf Dose 

(mg/kg/day)e MOEg

Mixing/Loading/Applying 

Liquids via Backpack 

Sprayer

Turf

8.26 4.12 0.00258

0.75 lb ai/A 5 A 0.095 110 0.047 210 0.00012 83,000 110 210

Golf Course 0.75 lb ai/A 5 A 0.095 110 0.047 210 0.00012 83,000 110 210

Drench Tree 

Treatments (8 inch 

Tree)

0.07 lb ai/tree 50 trees 0.089 110 0.044 230 0.00011 89,000 110 230

Drench Tree 

Treatments (35 inch 

Tree)

0.31 lb ai/tree 50 trees 0.39 26 0.2 51 0.0005 20,000 25 51

Foliar Sprays on 

Ornamentals in 

Nurseries and 

Greenhouses

11.2 6.23 0.14 0.59 lb ai/A 5 A 0.1 99 0.056 180 0.0052 1,900 94 160

Mixing/Loading/Applying 

Liquids via Manually 

Pressurized Handwand

Foliar Sprays on 

Ornamentals in 

Nurseries and 

Greenhouses

0.43 0.365 0.03

0.59 lb ai/A 5 A 0.0039 2,600 0.0033 3,000 0.0011 9,000 2,000 2,300

Drench Tree 

Treatments (8 inch 

Tree)

0.07 lb ai/tree 50 trees 0.0046 2,200 0.0039 2,600 0.0013 7,600 1,700 1,900

Drench Tree 

Treatments (35 inch 

Tree)

0.31 lb ai/tree 50 trees 0.02 490 0.017 580 0.0058 1,700 380 430

Mixing/Loading/Applying 

Liquids via Mechanically 

Pressurized Handwand

Turf 0.88 0.45 0.0019 0.75 lb ai/A 5 A 0.01 990 0.0052 1,900 0.000089 110,000 980 1,900

Golf Course 0.75 lb ai/A 5 A 0.01 990 0.0052 1,900 0.000089 110,000 980 1,900

Foliar Sprays on 

Ornamentals in 

Nurseries

0.39 0.29 0.0039 0.59 lb ai/A 25 A 0.018 570 0.013 760 0.00072 14,000 550 720

Foliar Sprays on 

Ornamentals in 

Greenhouses

2.5 1.6 0.12 0.59 lb ai/A 25 A 0.11 89 0.072 140 0.022 450 74 110

Loading/Applying 

Granulars via Push-type 

Spreader

Turf

0.24 0.13 0.01

0.5 lb ai/A 5 A 0.0018 5,400 0.001 10,000 0.00031 32,000 4,700 7,600

Golf Course 0.5 lb ai/A 5 A 0.0018 5,400 0.001 10,000 0.00031 32,000 4,700 7,600

a. Unit Exposures taken from Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (http://www.epa.gov/opp00001/science/handler-exposure-table.pdf)

b. Application rates = maximum application rates from labels.

c. Amount handled per day values are HED estimates of acres treated or gallons applied per day based on Exposure SAC SOP #9 “Standard Values for Daily Acres Treated in Agriculture,” industry 

sources, and HED estimates.

d. Dermal Dose (mg/kg/day) = Dermal Unit exposure (mg/lb ai) x App Rate x Area Treated x %Absorption (24.5% dermal) / Body weight (80 kg). 

e. Inhalation Dose (mg/kg/day) = Inhalation Unit exposure (mg/lb ai) x App Rate x Area Treated x %Absorption (100% inhalation ) / Body weight (80 kg). 

f. Dermal MOE = NOAEL (10 mg/kg/day) / Dermal Dose (mg/kg/day) 

g. Inhalation MOE = NOAEL (10 mg/kg/day) / Inhalation Dose (mg/kg/day) 
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8.1.2 Short- and Intermediate-Term Handler Risk for Seed Treatments

Paclobutrazol is currently registered for commercial seed treatment use on tomato, pepper, 

cucurbit, broccoli, cauliflower, and cabbage seeds (see Table 2.3). The paclobutrazol labels do 

not permit on-farm seed treatment. Based on the existing seed treatment use pattern, there is 

potential for exposure to paclobutrazol to primary handlers (i.e., activities related to treating the 

seed) and secondary handlers (i.e., planting treated seed). Primary and secondary handler 

exposure is expected to be short- or intermediate-term in duration based on information provided 

on the proposed label. The short- and intermediate-term toxicological endpoints are the same for 

the respective routes of exposure; therefore, the estimates of risk for short-term duration 

exposures are protective of those for intermediate-term durations.

Primary Handler (Treating Seed)

Potential primary occupational handler exposure scenarios from the use of paclobutrazol as a 

commercial seed treatment include:

Mixing, loading, applying liquid formulations;

Bagging treated seed;

Sewing bags; and

Multiple activities.

Typically, for large-scale commercial seed treatments, workers perform only those specific 

individual tasks listed above; however, it is assumed that workers also may perform multiple 

activities throughout the day. As a result a “multiple activities” scenario (i.e. where one worker 

performs all seed treatment tasks such as loading/applying, sewing, bagging, cleaning, 

calibration, repair, forklift driver, etc.) was addressed. No assessment was performed for onfarm seed treatment as the paclobutrazol labels do not permit on-farm seed treatment. 

Secondary Handler (Planting Treated Seed)

Potential secondary occupational handler exposure scenarios from the use of paclobutrazol as a 

commercial seed treatment include planting treated seed.

It is the policy of HED to use the best available data to assess handler exposure. Sources of 

generic handler data for seed treatment are incorporated in HED ExpoSAC Policy 14: SOPs for 

Seed Treatment. The amount of active ingredient handled depends on the application rate (lb 

ai/lb seed or lb ai/seed), the pounds of seed treated in a day, and the pounds of seed that can be 

planted in a day, all of which vary depending upon the seed type. Values for the amount of seed 

treated and planted per day were obtained from a Biological and Economic Analysis Division 

memo entitled, “Acres Planted per Day and Seeding Rates of Crops Grown in the United States” 

(J. Becker and S. Ratnayake; 3/24/11).

Summaries of the risk estimates for primary and secondary handlers are included in Tables 

8.1.2a and 8.1.2b, respectively. The short- and intermediate-term risk estimates for all primary 

and secondary handler scenarios do not exceed HED’s level of concern (MOEs > 1000) at some 

level of personal protective equipment (PPE).
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Table 8.1.2a: Summary of Short- and Intermediate-Term Occupational Handler Exposure and Risk Estimates for Paclobutrazol 

Seed Treatment Uses

Seed Type

lbs seed 

treated/day

a

Application 

Rate b

(lb ai/lb seed)

Amount 

Handled 

per day

(lb ai/day)

Baseline 

Dermal Unit 

Exposure c

(mg/lb ai)

Baseline 

Inhalation Unit 

Exposure c

(ug/lb ai)

PPE-G 

Dermal 

Unit 

Exposure c

(mg/lb ai)

Baseline 

Dermal 

MOE d

PPE-G 

Dermal 

MOE d

Baseline 

Inhalation 

MOE e

Total 

Baseline 

MOE

Total MOE 

(Baseline 

Inhalation + 

Gloves)

Loader/Applicator

Cucurbit

(Cucumber) 5512 0.000229 1.3

No Data 0.34 0.023

N/A 110000 1900000 N/A 100000

Cucurbit 

(Cantaloupe) 5512 0.00027 1.5 N/A 95000 1600000 N/A 90000

Cucurbit (Pumpkin) 5512 0.000107 0.6 N/A 240000 4000000 N/A 230000

Cucurbit (Squash) 5512 0.000172 0.9 N/A 150000 2500000 N/A 140000

Cucurbit 

(Watermelon) 5512 0.000157 0.9 N/A 160000 2700000 N/A 150000

Pepper 5512 0.00247 13.6 N/A 10000 170000 N/A 9400

Tomato 5512 0.00414 22.8 N/A 6200 100000 N/A 5800

Broccoli 5512 0.000661 3.65 N/A 39000 650000 N/A 37000

Cauliflower 5512 0.000635 3.5 N/A 41000 670000 N/A 39000

Cabbage 5512 0.000639 3.52 N/A 40000 670000 N/A 38000

Sewer

Cucurbit

(Cucumber) 5512 0.000229 1.3

0.0062 0.23 No Data

420000 N/A 2800000 360000 N/A

Cucurbit 

(Cantaloupe) 5512 0.00027 1.5 350000 N/A 2300000 300000 N/A

Cucurbit (Pumpkin) 5512 0.000107 0.6 890000 N/A 5900000 770000 N/A

Cucurbit (Squash) 5512 0.000172 0.9 560000 N/A 3700000 490000 N/A

Cucurbit 

(Watermelon) 5512 0.000157 0.9 610000 N/A 4000000 530000 N/A

Pepper 5512 0.00247 13.6 39000 N/A 260000 34000 N/A

Tomato 5512 0.00414 22.8 23000 N/A 150000 20000 N/A

Broccoli 5512 0.000661 3.65 140000 N/A 950000 120000 N/A

Cauliflower 5512 0.000635 3.5 150000 N/A 990000 130000 N/A

Cabbage 5512 0.000639 3.52 150000 N/A 990000 130000 N/A
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Table 8.1.2a: Summary of Short- and Intermediate-Term Occupational Handler Exposure and Risk Estimates for Paclobutrazol 

Seed Treatment Uses

Seed Type lbs seed 

treated/day a

Application 

Rate b

(lb ai/lb seed)

Amount 

Handled 

per day

(lb ai/day)

Baseline 

Dermal Unit 

Exposure c

(mg/lb ai)

Baseline 

Inhalation Unit 

Exposure c

(ug/lb ai)

PPE-G 

Dermal 

Unit 

Exposure c

(mg/lb ai)

Baseline 

Dermal 

MOE d

PPE-G 

Dermal 

MOE d

Baseline 

Inhalation 

MOE e

Total 

Baseline 

MOE

Total MOE 

(Baseline 

Inhalation 

+ Gloves)

Bagger

Cucurbit

(Cucumber) 5512 0.000229 1.3

0.0091 0.16 No Data

280000 N/A 4000000 260000 N/A

Cucurbit 

(Cantaloupe) 5512 0.00027 1.5 240000 N/A 3400000 220000 N/A

Cucurbit (Pumpkin) 5512 0.000107 0.6 610000 N/A 8500000 570000 N/A

Cucurbit (Squash) 5512 0.000172 0.9 380000 N/A 5300000 350000 N/A

Cucurbit 

(Watermelon) 5512 0.000157 0.9 410000 N/A 5800000 380000 N/A

Pepper 5512 0.00247 13.6 26000 N/A 370000 24000 N/A

Tomato 5512 0.00414 22.8 16000 N/A 220000 15000 N/A

Broccoli 5512 0.000661 3.65 98000 N/A 1400000 91000 N/A

Cauliflower 5512 0.000635 3.5 100000 N/A 1400000 93000 N/A

Cabbage 5512 0.000639 3.52 100000 N/A 1400000 93000 N/A

Multiple Activities

Cucurbit

(Cucumber) 5512 0.000229 1.3

No Data 1.6 0.042

N/A 62000 400000 N/A 54000

Cucurbit 

(Cantaloupe) 5512 0.00027 1.5 N/A 52000 340000 N/A 45000

Cucurbit (Pumpkin) 5512 0.000107 0.6 N/A 130000 850000 N/A 110000

Cucurbit (Squash) 5512 0.000172 0.9 N/A 82000 530000 N/A 71000

Cucurbit 

(Watermelon) 5512 0.000157 0.9 N/A 90000 580000 N/A 78000

Pepper 5512 0.00247 13.6 N/A 5700 37000 N/A 4900

Tomato 5512 0.00414 22.8 N/A 3400 22000 N/A 2900

Broccoli 5512 0.000661 3.65 N/A 21000 140000 N/A 18000

Cauliflower 5512 0.000635 3.5 N/A 22000 140000 N/A 19000

Cabbage 5512 0.000639 3.52 N/A 22000 140000 N/A 19000

a HED default for lb seed treated per day from HED Exposure Science Advisory Council Policy 15.

b Application Rates based on existing labels for paclobutrazol.

c Unit Exposures from HED Exposure Science Advisory Council Policy 14.

d Dermal Dose (mg/kg/day) = dermal unit exposure (mg/lb ai) x application rate (lb ai/lb seed) x amount treated (lb seed/day) x absorption factor (24.5%) / body weight (80 kg 

adult). Dermal MOE = NOAEL (10.0 mg/kg/day for short- and intermediate-term exposure) / Dermal Dose (mg/kg/day). Level of concern = 1000.

e Inhalation Dose (mg/kg/day) = inhalation unit exposure (mg/lb ai) x application rate (lb ai/lb seed) x amount treated (lb seed/day) x absorption factor (100%) / body weight (80 

kg adult). Inhalation MOE = NOAEL (10.0 mg/kg/day for short- and intermediate-term exposure) / Inhalation Dose (mg/kg/day). Level of concern = 1000.
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Table 8.1.2b: Summary of Secondary Handler (Planter) Exposures and Risks for Paclobutrazol

Crop

Application 

Rate a

(lb ai/lb seed)

Seeds/lb b seeds 

planted/acre b

lbs 

seed/acre

Amount 

Handled per 

day c

(lb ai/day)

PPE-G Dermal 

Unit Exposure 

(mg/lb ai) d

Baseline 

Inhalation Unit 

Exposure

(ug/lb ai) d

PPE-G 

Dermal 

MOE e

Baseline 

Inhalation 

MOE f

Total MOE 

(Baseline 

Inhalation + 

Gloves)

Cucurbit Seed 

(Cucumber) 0.000229 12000 139392 11.6 0.21 0.25 3.4 61000 1100000 58000

Cucurbit Seed 

(Cantaloupe) 0.00027 16000 38848 2.4 0.052 0.25 3.4 250000 4500000 240000

Pepper 0.00247 50000 69696 1.4 0.28 0.25 3.4 47000 850000 45000

Cucurbit Seed 

(Pumpkin) 0.000107 1600 7260 4.5 0.039 0.25 3.4 340000 6100000 320000

Cucurbit Seed 

(Squash) 0.000172 1920 15374 8.0 0.11 0.25 3.4 120000 2100000 110000

Cucurbit Seed 

(Watermelon) 0.000157 4800 43560 9.1 0.11 0.25 3.4 110000 2100000 100000

Tomato 0.00414 120000 130680 1.1 0.36 0.25 3.4 36000 650000 34000

Broccoli 0.000661 80000 210845 2.6 0.1394 0.25 3.4 94000 1700000 89000

Cauliflower 0.000635 80000 23232 0.3 0.0148 0.25 3.4 890000 16000000 840000

Cabbage 0.000639 45000 98010 2.2 0.1113 0.25 3.4 120000 2100000 110000

a Application Rates based on existing labels for paclobutrazol.

b Taken from a Biological and Economic Analysis Division memo entitled, “Acres Planted per Day and Seeding Rates of Crops Grown in the United States” (J. Becker and S. 

Ratnayake; 3/24/11).

c Amount Handled per Day = Application Rate (lb ai/seed) * lbs seed/acre * 80 acres.

d Unit Exposures from HED Exposure Science Advisory Council Policy 14. No data is available for baseline dermal exposure (i.e., no gloves).

e Dermal Dose (mg/kg/day) = dermal unit exposure (mg/lb ai) x application rate (lb ai/lb seed) x amount treated (lb seed/day) x absorption factor (24.5%) / body weight (80 kg 

adult). Dermal MOE = NOAEL (10.0 mg/kg/day for short- and intermediate-term exposure) / Dermal Dose (mg/kg/day). Level of concern = 1000.

f Inhalation Dose (mg/kg/day) = inhalation unit exposure (mg/lb ai) x application rate (lb ai/lb seed) x amount treated (lb seed/day) x absorption factor (100%) / body weight (80 

kg adult). Inhalation MOE = NOAEL (10.0 mg/kg/day for short- and intermediate-term exposure) / Inhalation Dose (mg/kg/day). Level of concern = 1000.
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8.2 Occupational Post-Application Exposure and Risk

8.2.1 Postapplication Inhalation Exposure

Based on the Agency's current practices, a quantitative postapplication inhalation exposure 

assessment was not performed for paclobutrazol at this time primarily because paclobutrazol’s 

vapor pressure (1.28 x 10-9mm Hg @ 25.0°C) and Henry's Law Constant (8.09 x 10-10 atm 

m

3

/mol) indicate that the compound is relatively non-volatile under field conditions. However, 

there are multiple potential sources of post-application inhalation exposure to individuals 

performing post-application activities in previously treated fields. These potential sources 

include volatilization of pesticides and resuspension of dusts and/or particulates that contain 

pesticides. The Agency sought expert advice and input on issues related to volatilization of 

pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel 

(SAP) in December 2009, and received the SAP’s final report on March 2, 2010 

(http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The Agency is in the 

process of evaluating the SAP report as well as available post-application inhalation exposure 

data generated by the Agricultural Reentry Task Force and may, as appropriate, develop policies 

and procedures, to identify the need for and, subsequently, the way to incorporate occupational 

post-application inhalation exposure into the Agency's risk assessments. If new policies or 

procedures are put into place, the Agency may revisit the need for a quantitative occupational 

post-application inhalation exposure assessment for paclobutrazol.

8.2.2 Postapplication Dermal Exposure

Based on the existing paclobutrazol use pattern (see Table 2.3), HED expects the occupational 

postapplication to occur in two ways: contact with treated turf on golf courses and contact with 

treated ornamentals in greenhouses and nurseries. Dermal exposures during postapplication 

activities were estimated using 1) standard default values for dermal transfer coefficients from 

the Science Advisory Council for Exposure Policy Number 3.2: Agricultural Transfer 

Coefficients, June 3, 2011, 2) a TTR study (discussed above in Section 5.2), and 3) two 

chemical-specific dislodgeable foliar residue (DFR) studies (Bonzi® on Chrysanthemums: 

Dislodgeable Foliar Residue Study – MRID No.: 45310801 and Bonzi® on Poinsettias: 

Dislodgeable Foliar Residue Study – MRID No.: 45336601) submitted in support of the existing 

paclobutrazol uses. HED used both of the DFR studies to analyze postapplication exposures to 

paclobutrazol resulting from contact with treated ornamentals in greenhouses and nurseries.

A summary of the postapplication exposure and risk estimates resulting from use of 

paclobutrazol is provided in Table 8.2.2. The short- and intermediate-term risk estimates for golf 

course maintenance activities do not exceed HED’s level of concern (MOEs > 1000) using 

predicted Day 0 residue values form the TTR study. The short- and intermediate-term risk 

estimates for ornamentals in greenhouses and nurseries do not exceed HED’s level of concern 

(MOEs > 1000) using predicted Day 0 residue values from either the Chrysanthemum or 

Poinsettia DFR data for all activities except for hand set irrigation. Hand set irrigation would not 

be performed in greenhouses and thus this issue only applies to nursery situations.
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Table 8.2.2: Summary of Short-and Intermediate-term Occupational Post-Application Risks for 

Paclobutrazol

Crop/Site Activities

Transfer 

Coefficient 

(cm2/hr)

Application 

Rate

(lb ai/A)

Predicted 

Day 0 TTR 

or DFR 

(ug/cm2)

Day 0 Dermal 

Dose

(mg/kg/day) d

Day 0 

MOE e

Day X at 

which MOE 

>= LOC

Turf a golf course 

maintenance 3,700 0.75 0.077 0.007 1500 N/A

Ornamentals in 

Greenhouse and Nurseries 

using Chrysanthemum 

DFR Data b

transplanting, 

irrigation, hand 

harvesting, container 

moving, hand weeding, 

pinching, tying/ 

training, propagating, 

hand pruning

230 0.59 0.68 0.0041 2,500 N/A

Irrigation (hand set) f1900 0.59 0.68 0.034 300 40

Ornamentals in 

Greenhouse and Nurseries 

using Poinsettia DFR 

Data c

transplanting, 

irrigation, hand 

harvesting, container 

moving, hand weeding, 

pinching, tying/ 

training, propagating, 

hand pruning

230 0.59 0.47 0.0027 3800 N/A

Irrigation (hand set) f1900 0.59 0.47 0.022 460 6

a. TTR data represents CA which was the test site with the highest residues.

b. Chrysanthemum DFR data represents use in a greenhouse in Oregon.

c. Poinsettia DFR data represents use in a shadehouse in Florida

d. Dermal Dose = [DFR or TTR (ug/cm2) x Tc (cm2/hr) x 0.001 mg/ug x 8 hrs/day x DAF (24.5%)] body weight (80 kg)

e. Dermal MOE = NOAEL (10 mg/kg/day)/ Dermal Dose (mg/kg/day). 

f. Hand set irrigation only applies to nursery settings.

Restricted Entry Interval

The restricted entry interval (REI) listed on the existing paclobutrazol labels is based on the 

acute toxicity of the technical material. Paclobutrazol is classified as Toxicity Category II for 

acute dermal toxicity and Toxicity Category III for eye and skin irritation. It is not a dermal 

sensitizer (Category IV). In accordance with the Worker Protection Standard (WPS), acute 

Toxicity Category III and II chemicals require a 24- or 12- hour REI, respectively. Furthermore, 

based on the occupational postapplication assessment, most postapplication dermal risk estimates 

do not exceed HED’s level of concern (MOEs > 1000). Based on the acute dermal toxicity, the 

12-hour REI that appears on the current paclobutrazol labels may not be adequate and should be 

revisited. Special consideration should also be given to use of hand set irrigation in nurseries.
Paclobutrazol Human Health Risk Assessment DP No. 394230

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9.0 References

Becker, J. and S. Ratnayake. (2011). Acres Planted per Day and Seeding Rates of Crops Grown 

in the United States.

Doherty, M., et al. (2006). 1,2,4-Triazole, Triazole Alanine, Triazole Acetic Acid: Human 

Health Aggregate Risk Assessment in Support of Reregistration and Registration Actions for 

Triazole-derivative Fungicide Compounds. DP Number: D322215, dated February 7, 2006.

Hurley , P. (1994). Toxicology Endpoint Selection Document, dated 04/11/1994, TXR No. 

013485.

Ghali, G. (1994). RfD/Peer Review Report of Paclobutrazol dated June 23, 1994, TXR No. 

011081. 

Morton, T. (2012). Common Triazole Metabolites: Updated Aggregate Human Health Risk 

Assessment to Address The Amended Propiconazole Section 3 Registration to Add Uses on 

Snap beans, succulent shelled beans, dry beans, tomato (post-harvest, citrus (post-harvest), and 

stone fruit (post-harvest); The Amended Difenoconazole Section 3 Registration to Add Use on 

Potato; and the Flutriafol Section 3 Registration to Add Use on Field Corn and the Section 18 

Use on Cotton. DP Number: D397592, dated January 26, 2012.

Reaves, E. and C. Smith. (2007). Paclobutrazol: Registration Review Scoping Document for 

Human Health Assessments. PC Code: 125601; DP Number: D335538, dated March 13, 2007. 

Smegal, D. (2012). Paclobutrazol: Summary of Hazard and Science Policy (HASPOC) Meeting 

of December 8, 2111: Recommendations on data requirements for immunotoxicity and acute 

and subchronic neurotoxicity studies for paclobutrazol dated January 3, 2012, TXR No. 

0056149. 
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Appendix A: Paclobutrazol Toxicity Profiles

A.1 Toxicology Data Requirements

The toxicological data requirements (40 CFR 158.340) for non-food uses for paclobutrazol are 

listed in Table A.1. Use of the new guideline numbers does not imply that the new (1998) 

guideline protocols were used. 

Table A.1 Test Required for Nonfood Use Pesticides Technical

Required Satisfied

870.1100 Acute Oral Toxicity ........................................................

870.1200 Acute Dermal Toxicity ...................................................

870.1300 Acute Inhalation Toxicity ...............................................

870.2400 Primary Eye Irritation .....................................................

870.2500 Primary Dermal Irritation ...............................................

870.2600 Dermal Sensitization.......................................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.3100 Oral Subchronic (rat)......................................................

870.3150 Oral Subchronic (dog) ....................................................

870.3200 21/28-Day Dermal (rat) ..................................................

870.3250 90-Day Dermal ...............................................................

870.3465 28-Day Inhalation ...........................................................

yes

no

no

yes

CR

yes

no

yes

yes

---

870.3700a Developmental Toxicity (rat) .........................................

870.3700b Developmental Toxicity (rabbit) ....................................

870.3800 Reproduction (rat)...........................................................

yes

yes

yes

yes

yes

yes

870.4100a Chronic Toxicity (rat).....................................................

870.4100b Chronic Toxicity (dog) ...................................................

870.4200a Carcinogenicity (rat).......................................................

870.4200b Carcinogenicity (mouse).................................................

870.4300 Chronic/Carcinogenicity (rat).........................................

CR

yes

CR

CR

CR

yes

yes

no

no

no

870.5100 Mutagenicity—Gene Mutation - bacterial......................

870.5300 Mutagenicity—Gene Mutation - mammalian.................

870.5375 Mutagenicity—Structural Chromosomal Aberrations....

870.5395 Mutagenicity—Mammalian Erythrocyte Micronucleus.

870.5450 Mutagenicity—Rodent dominant lethal assay 

870.5500 Mutagenicity— Bacterial DNA Damage or Repair Test

870.5550 Mutagenicity—Unscheduled DNA Synthesis.................

yes

yes

yes

yes

no

no

no

yes

yes

yes

yes

yes

yes

yes

870.6100a Acute Delayed Neurotoxicity. (hen)...............................

870.6100b 90-Day Neurotoxicity (hen)............................................

870.6200a Acute Neurotoxicity Screening Battery (rat) ..................

870.6200b 90 Day Neurotoxicity Screening Battery (rat) ................

870.6300 Developmental Neurotoxicity (rat).................................

no

no

yes

yes

CR

no

no

no1

no

no

870.7485 General Metabolism (rat)................................................

870.7600 Dermal Penetration, in vivo (male rat)............................

yes

yes

yes

yes

870.7800 Immunotoxicity (rat and mouse)........................... yes no

1 The ACN study has recently been submitted to the Agency and is under review.
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Appendix A.2. Toxicity Profiles

A.2 Toxicity Profiles

The toxicological data for the acute toxicity studies with paclobutrazol are listed on Table 

A.2.1.

Table A2.1: Acute Toxicity of Paclobutrazol Technical Grade

Guideline No/Study Type MRIDs Results Toxicity Category

870.1100 Acute Oral (97% ai)

Alderley Park Rat 00117478 (1983) LD50 = 1954 mg/kg (M)1336 mg/kg (F) III

870.1100 Acute Oral (97% ai)

Alderley Park Mouse 00117478 (1982) LD50 = 490 mg/kg (M)1219 mg/kg (F) II

870.1100 Acute Oral (97% ai)

Dunkin Hartley Albino Guinea pig 00117478 (1982) LD50 = 542 mg/kg (M)>400 and <640 mg/kg (F) III

870.1100 Acute Oral (97% ai)

NZW Rabbit

00117478 (1982) LD50 = 835 mg/kg (M)

937 mg/kg (F) III

870.1200 Acute Dermal (97% ai) 

Alderley Park Rat 00117478 (1982) LD50 = >1000 mg/kg

(M F) II

870.1200 Acute Dermal (97% ai) 

NZW Rabbit 00117478 (1982) LD50 = >1000 mg/kg(M F) II

870.1300 Acute Inhalation (97% ai)

50% ai Alderley Park Rat

00117482 (1982) LC50 = >766 mg/m3 (M)

359-766 mg/m3 (F) II

870. 2400 Primary Eye Irritation (97% ai)

NZW Rabbit

00117479 (1982)

5/6 rabbits with unwashed eyes 

had slight corneal opacity, 

which cleared within 7 days; 

3/6 rabbits with washed eyes 

had slight redness of the 

conjunctiva, with some 

chemosis and discharge, which 

was not apparent by 3 days.

IIIa

870.2500 Primary Skin Irritation 

(97% ai) NZW Rabbit 00117479 (1982) Mild irritation that persisted for 

72 hours III

870.2500 Primary Skin Irritation 

(97% ai) Alderley Park 

Albino Rat

00117479 (1982)

3/5 M showed erythema; 2/5 (F) 

showed desquamation and 

scabbing. Effects did not 

persist in either sex.

III

870.2600 Dermal Sensitization (Guinea 

pig) Dunkin Hartley Albino 00117479 (1982) Not a skin sensitizer

a Reclassified in 1995, based on additional data provided by the registrant (HED Document 011460). 
Paclobutrazol Human Health Risk Assessment DP No. 394230

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Table A.2.2: Toxicity Profile of Paclobutrazol Technical

Guideline No./

Study Type

MRID No. (year)/ 

Classification/Doses Results

870.3100

90-Day oral toxicity

rodents (rat)

00132689 (1983)/

47338506 (2007)

Acceptable/guideline

0, 50, 250 or 1250 ppm 

[equivalent to 0, 3.7, 18.8 

or 93.0 mg/kg/day (M) 

0, 4.4, 21.6 or 106.5 

mg/kg/day (F)]a.

NOAEL =18.8 mg/kg/day for both sexes 

LOAEL = 93.0 mg/kg/day, based on elevated liver 

weights, serum cholesterol, hepatic aminopyrene-Ndemethylase activity and alanine transaminase levels in 

females.

870.3150

6-Week oral toxicity

in dogs 

00132690 (1983)

Unacceptable

0, 15, 75, or 225 

mg/kg/day (M & F).

NOAEL = 15 mg/kg/day (LDT)

LOAEL = 75 mg/kg/day, based on increased liver 

weights and serum alkaline phosphatase levels. Only 1 

M and 1 F tested at each level.

870.3200 

21/28-Day dermal toxicity

(rabbit)

00132688 (1980)

Acceptable/guideline

0, 10, 100, or 1000 

mg/kg/day, 6 hrs/day for 5 

d/week during a 21-day 

period.

NOAEL =10 mg/kg/day (intact skin)

LOAEL = 100 mg/kg/day, based on irritation at all 

doses with abraded skin and at 100 and 1000 

mg/kg/day with intact skin. Irritation began to appear 

during 2nd week of application. Degree increased with 

increasing dose. Hyperkeratosis, acanthosis and 

inflammatory changes of superficial dermis. 

870.3700a

Prenatal developmental 

toxicity in rodents

(Wistar rats, derived from 

Alderly Park strain)

00132693 (1983)

Acceptable/guideline

0, 40, 100, or 250 

mg/kg/day from days 6 

through 15 of gestation. 

Maternal NOAEL = 40 mg/kg /day (LDT).

LOAEL =100 mg/kg /day, based on decreased body 

weight gain and food utilization efficiency during 

dosing. Mortality (5/24) and grossly observable liver 

pallor and enlargement at 250 mg/kg/day (HDT)

Developmental NOAEL = 40 mg/kg /day. LOAEL 

=close to 40 but set at 100 mg/kg/day, based on delayed 

ossification and partial ossification of odontal bone at 

100 and 250 mg/kg/day. Delayed ossification 

statistically significant for fetuses at 40 mg/kg/day but 

not for litters. Partial ossification of occipital bone at 

250 mg/kg/day. Cleft palate in 3 fetuses from 2 litters 

at 250 mg/kg/day.

870.3700a

Prenatal developmental 

toxicity in rodents

(Wistar rats, derived from 

Alderly Park strain)

00143158 (1984)

Acceptable/guideline

0, 2.5, 10, 40, or 100 

mg/kg/day from days 7 

through 16 of gestation.

Maternal NOAEL = >100 mg/kg /day (HDT).

Developmental NOAEL = 10 mg/kg /day. LOAEL = 

40 mg/kg/day, based on renal dilation, hydroureter and 

minor skeletal defects or variations. 

870.3700b

Prenatal developmental 

toxicity in nonrodents

(NZW rabbit)

00132692 (1983)

Unacceptable

0, 25, 75, or 125 

mg/kg/day from days 6 

through 18 of gestation. 

Maternal NOAEL =75 mg/kg /day 

LOAEL = 125 mg/kg/day, based on decreased body 

weight gain during dosing. Low fertility; only low and 

mid-dose groups had > minimum number of litters 

at sacrifice.

Developmental NOAEL = None observed

870.3700b 40734302 (1986) Maternal NOAEL = 75 mg/kg /day 
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Table A.2.2: Toxicity Profile of Paclobutrazol Technical

Guideline No./

Study Type

MRID No. (year)/ 

Classification/Doses Results

Prenatal developmental 

toxicity in nonrodents

(NZW rabbit)

Acceptable/guideline

0, 25, 75, or 125 

mg/kg/day from days 7

through 19 of gestation.

LOAEL = 125 mg/kg/day, based on decreased body 

weights and food consumption during dosing. 

Developmental NOAEL = 75 mg/kg/day

LOAEL = 125 mg/kg/day, based on the increased 

incidence of extra ribs in pups.

870.3800

Reproduction and fertility 

effects

(rat)

40734303 (1987)/ 

47338506 (2007)

Acceptable/guideline

0, 50, 250 and 1250 ppm 

in the diet [equivalent to 

0, 4.8, 24.4, and 121.2 

mg/kg/day (F0 M); 0, 5.1, 

25.9 and 126.2 (F0 F); 0, 

4.7, 23.2 and 116.9 (F1

M); and 0, 5.1, 24.8 and 

124.1 mg/kg /day (F1 F)]a

Parental systemic NOAEL = 23.2 mg/kg /day 

LOAEL = 116.9 mg/kg/day, based on the increases in 

liver weights and fatty changes and thickening of the 

urinary bladder walls in females 

Reproductive NOAEL = 116.9 mg/kg/day (HDT) 

LOAEL = N/A

Offspring NOAEL =23.2 mg/kg /dayb

LOAEL= 116.9 mg/kg/day, based on the increased 

incidence of chromodacryorrhea, thickened eyelids and 

dental malocclusion, increased liver weights, mottling 

or accentuation of the lobular structure of the liver, 

along with liver enlargement, pallor and discoloration.

870.4100a

Chronic toxicity

(rat)

40734301 (1986)/

47078901 (2007)

Acceptable/guideline

0, 50, 250 or 1250 ppm 

[equivalent to 0, 2.2, 10.8, 

54.2 mg/kg/day (M) & 0, 

2.8, 14.0, 72.1 mg/kg/day 

(F) for 2 years] a

NOAEL = 10.8 mg/kg/day 

LOAEL. = 54.2 mg/kg/day based on an increase in 

hypertrophy/steatosis of the liver (both sexes), 

decreased triglycerides (females) and increased liver 

weights (both sexes). Possible borderline increase in 

uterine stromal polyps in high and mid-dose females. 

870.4100b

Chronic toxicity 

(dog)

00132691/00143166 

(1986)

Acceptable/guideline

0, 15, 75 or 300 

mg/kg/day) for 1 year.

NOAEL =15 mg/kg/day 

LOAEL = 75 mg/kg/day, based on elevated serum 

alkaline phosphatase and triglycerides levels, enlarged 

hepatic cells, increased liver weights, and increased 

hepatic aminopyrine N-demethylase activity. 

870.4200a

Carcinogenicity 

(rat)

See 870.4100a

40762501 (1986)

Unacceptable

Maximum tolerated dose (MTD) was not achieved and 

possible positive response for uterine stromal polyps.
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Table A.2.2: Toxicity Profile of Paclobutrazol Technical

Guideline No./

Study Type

MRID No. (year)/ 

Classification/Doses Results

870.4200b

Carcinogenicity 

(mouse)

40762501 (1986)

Acceptable/guideline 

(Chronic phase)

0, 25, 125, or 750 ppm 

(equivalent to 0, 3.75, 

18.75 or 112.5mg/kg /day 

for 104 weeks. 

Unacceptable 

(Carcinogenicity phase) 

NOAEL =125 ppm (18.85 mg/kg/day both sexes). 

LOAEL = 750 ppm (112.5 mg/kg/day both sexes), 

based on increased severity of steatosis of the liver in 

males, decreased triglycerides and cholesterol (males) 

and increased absolute & relative liver weights (M & 

F). 

Borderline increase in Leydig cell tumors in high dose 

males with a significant (p<0.05) pairwise comparison 

and a significant (p<0.05) trend.

However, the high dose is considered inadequate 

because of the minimal toxicity at this level

.

870.5100

Bacterial reverse mutation 

(Ames Assay)

00017480 (1982)

1.6-5000 μg/plate +/-S9

Acceptable/guideline

Negative up to 5,000 μg/plate.

870.5300

In vitro mammalian cell gene 

mutation (mouse lymphoma 

cells)

00132695 (1983)

1.0-100 μg/mL –S9; 60-

140 μg/mL +S9

Acceptable/guideline

Negative up to cytotoxic doses. 

870.5375

In vivo chromosome 

aberration (rat bone marrow)

00143156 (1984)

0, 30, 150 or 300 mg/kg/ 

oral gavage

Acceptable/guideline

Negative; no clastogenic effects at any dose tested. 

870.5395

Mammalian erythrocyte 

micronucleus assay (mouse)

00132694 (1983)

0, 87.5 or 140 mg/kg /ip

Acceptable/guideline

Negative up to 50 or 80% of the LD50 via ip injection.

870.5450

Rodent dominant lethal test 

(mouse)

00143155 (1983)

0, 25, 1000 or 300 

mg/kg/day X 5 days/oral 

gavage

Acceptable/guideline

Negative for dominant lethal mutations.

870.5550

In vivo unscheduled DNA 

synthesis (UDS, rat 

hepatocytes)

40734304 (1986)

0, 40, 200 or 400 mg/kg 

Acceptable

Negative, no induction of UDS

870.6200a

Acute neurotoxicity 

screening battery (rat)

Not available

870.6200b

90 Day neurotoxicity 

screening battery (rat)

Not available

870.7485

General Metabolism 

(rat)

00132696 (1983)

Nonguideline

M&F: 10 mg/kg single 

gavage dose

During the 4 days following administration, 39.18 and 

52.6 % of the dose was recovered in the urine of male 

and female rats, respectively. Fecal recoveries were 

53.49% in the males and 37% in females. 

Approximately 60% of the administered dose was 
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Table A.2.2: Toxicity Profile of Paclobutrazol Technical

Guideline No./

Study Type

MRID No. (year)/ 

Classification/Doses Results

accounted for in feces and urine of males and females 

during the first 24 hours of dosing. Residue 

concentrations in tissues 3 or 4 days after dosing did 

not indicate accumulation, and urinary excretion along 

with slow fecal excretion indicated a significant 

gastrointestinal absorption of the dose. 

870.7485

General Metabolism 

(rat)

00143161 (10/1983)

Acceptable/guideline

5 mg/kg (single oral 

gavage)

70-80% of the 5 mg/kg dose was excreted during 72 

hours after dosing. Approximately 55% of the dose 

was recovered in the urine of both sexes, and 32% or 

24% was recovered in the feces of males and females, 

respectively. 7 days after dosing, liver tissue contained 

0.017 to 0.028 ppm; gastrointestinal tract contained 

0.012-0.025 ppm. No other tissue levels were 

detectable.

870.7485

General Metabolism 

(rat)

00143162 (2/1984)

Acceptable/guideline

250 mg/kg

70-80% of the 250-mg/kg dose was excreted during 

first 72 hours after dosing. Approximately 40% of the 

dose was excreted in urine from males and 30% from 

females. Approximately 30% and 40% of the dose was 

recovered in the feces of males and females, 

respectively after 72 hours. Gastrointestinal contents 

had 0.303 (♂) and 1.461 ppm (♀); liver samples 

contained from 0.444 to 0.848 ppm. 

870.7485

General Metabolism 

(rat)

00143160 (5/1984)

Acceptable/guideline

5 and 250 mg/kg (dose 

selection study for MRID 

00143160

A single dose of 250 mg/kg increased the liver weight, 

and the 5 mg/kg dose had no effect. These results were 

used as the basis for doses selection. 
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Table A.2.2: Toxicity Profile of Paclobutrazol Technical

Guideline No./

Study Type

MRID No. (year)/ 

Classification/Doses Results

870.7485

General Metabolism 

(Bioaccumulation in rat)

00143160 (5/1984)

Acceptable/guideline

250 mg/kg (single oral 

gavage)

Autoradiographs indicated that the liver, kidneys, and 

gastrointestinal tract contained the administered 

radiolabel. Similarly, the disposition of the 14c label 

after a single oral dose of 250 mg/kg is limited to the 

gastrointestinal contents and to a lesser extent to the 

liver and kidneys. 

870.7485

General Metabolism 

(rat)

EPA Accession No. 

254865 (5/1984)

Acceptable/guideline

5 mg/kg (oral gavage)

Concentrations of radiolabel plateaued in livers and 

kidneys after 28 days consecutive daily 5 mg/kg doses. 

Maximum levels: 2.22-2.55 ppm in liver and approx. 1 

ppm in kidney. Blood levels rose throughout the 49-

day dosing period (max. level = 0.158 ppm). Levels in 

fat were below the limit of detection (0.081 ppm) at 

most observations, and ranged from 0.046-0.148 ppm 

at other observations. Elimination of radioactivity from 

the livers and kidneys occurred in a biphasic manner. 

Half times for the first phase were 1.36 & 1.56 days for 

liver & kidney, respectively. Times for the 2nd phase 

were 6.69 and 9.26 days, respectively.

870.7485

General Metabolism 

(rat)

00143165 (5/1984)

Acceptable/guideline

5 or 250 mg/kg (single 

oral gavage)

A single oral gavage dose (5 or 250 mg/kg) 

paclobutrazol was absorbed almost completely by male 

and female rats. Triazole and halogenated phenyl 

moieties not affected in rat. Pentanol moiety oxidized 

to a diol or carboxylic acid & excreted in free or 

conjugated forms. Males excreted more of carboxylic 

acid metabolites than females but proportion of acid 

metabolites excreted by females increased as dose 

decreased. Approx. 75% of dose was recovered in bile 

during first 48 hours after dosing in males, and 50% is 

recovered from females during first 72 hours. 

870.7485

General Metabolism 

(dog)

00143163 (1984)

Acceptable/guideline

5 mg/kg (single oral 

gavage)

80-85% of 5 mg/kg dose extracted during first 24 hours 

after dosing. Approx. 50% of dose recovered in urine 

of both sexes, & 35-40% recovered in feces. Peak 

blood levels at 1 hour after dosing (4.1-4.4 ppm in 

plasma) declined to pre-dose levels 24-48 hours after 

treatment. No detectable levels in tissue & no sex 

differences were observed. 

870.7600

Dermal penetration (Rat)

41048202

0.011 mg/kg on an area 10 

cm2/rat

Acceptable/guideline

The highest % dose absorbed and remaining on the 

washed application site was 15.1% (10 hours) and 

24.5% (24 hours), respectively.

870.7800

Immunotoxicity Not available
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Appendix A.3. Hazard Identification and Endpoint Selection

A.3 .1 Acute Reference Dose (aRfD) – Females age 13-49/ General Population: None

As shown in Table A. 4, no appropriate endpoint attributable to a single dose was found in the 

available database, including the four developmental studies (2 in rats and 2 in rabbits). 

A.3.2. Chronic Reference Dose (cRfD)

Study Selected: Two-year chronic/carcinogenicity feeding study in rats 870.4300a [§83-5]

MRID No. 40734301

Dose and Endpoint for Risk Assessment: NOAEL = 10.8 mg/kg/day 

Comments About Study/Endpoint/Uncertainty Factors: For the chronic dietary risk 

assessment, the 2-year chronic/carcinogenicity feeding study in rats, with a NOAEL of 10.8 

mg/kg/day, was selected because it was near the lowest NOAEL in the most sensitive species 

and more appropriately covers the exposure duration of concern. An Uncertainty Factor (UF) of 

1000 was applied to account for both the interspecies extrapolation (10X) and intraspecies 

variability (10X) and the lack of data for neurotoxicity (acute and subchronic) and 

immunotoxicity (10X). On this basis, the cRfD was calculated to be 0.01 mg/kg/day.

Chronic RfD = 10.8 mg/kg/day (NOAEL) = 0.01 mg/kg/day

 1000 (UF)

A.3. 3 Incidental Oral Exposure: Short- (1-30 days) and Intermediate-term (1-6 months)

Study Selected: 90-day oral toxicity in rats 870.3100 [§82-1]

MRID No. 00132689

Dose and Endpoint for Risk Assessment: NOAEL = 18.8 mg/kg/day 

Comments About Study/Endpoint/Uncertainty Factors: The 90-day subchronic oral toxicity 

test in rats was selected for these scenarios because the endpoint of concern is appropriate for the 

population (infants and children) and the duration of the study covers the period of concern 

(short and intermediate term) for these exposures. The NOAEL for this study is 18.8 mg/kg/day; 

the LOAEL is 93.0 mg/kg/day, based on elevated liver weights and changes in clinical chemistry 

parameters associated with the liver. An MOE of 1000 is required which includes the 

interspecies extrapolation (10X) and intraspecies variability (10X) and the lack of data for 

neurotoxicity (acute and subchronic) and immunotoxicity (10X).
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A.3.4. Dermal Exposure: Short- (1-30 days) and Intermediate-term (1-6 months)

Study Selected: Prenatal developmental study in rats 870.3700a [§83-3]

MRID No. 00143158

Dose and Endpoint for Risk Assessment: NOAEL = 10 mg/kg/day 

Comments About Study/Endpoint/Uncertainty Factors: The original study considered for 

these exposure scenarios was the 21-day dermal study in rabbits with a NOAEL of 10 

mg/kg/day. However, the LOAEL (100 mg/kg/day) was based solely on irritation, which is not 

considered an appropriate endpoint for occupational or residential exposure. The Agency prefers 

to mitigate irritation through product labeling and the use of gloves and/or other protective 

clothing, which minimizes dermal contact. To safeguard against residential exposure via turf, 

the developmental study in rats (MRID 00143158) was selected to protect children playing on 

the lawn. The NOAEL for this study is 10 mg/kg/day; the LOAEL is 40 mg/kg/day, based on 

renal dilation, hydroureter and minor skeletal defects or variations. If the dermal absorption 

factor [25.4% for the 24-hour exposure, from the data in a dermal penetration study (MRID 

41048202)], were applied, the derived dermal equivalent dose (DED) would be 40.8 mg/kg/day. 

This dose would be protective of the potential pregnant population (females 13-49) as well as 

irritation seen following dermal application. An MOE of 1000 is required which includes the 

interspecies extrapolation (10X) and intraspecies variability (10X) and the lack of data for 

neurotoxicity (acute and subchronic) and immunotoxicity (10X).

A.3.5. Inhalation Exposure: Short- (1-30 days) and Intermediate-term (1-6 months)

Study Selected: Prenatal developmental study in rats 870.3700a [§83-3]

MRID No. 00143158

Dose and Endpoint for Risk Assessment: NOAEL = 10 mg/kg/day 

Comments About Study/Endpoint/Uncertainty Factors: Since a repeated dose inhalation 

study was not available, an oral NOAEL was selected for this risk assessment. See Section A.3.4. 

Since an oral dose was selected absorption via inhalation is presumed to be equivalent to oral 

absorption. An MOE of 1000 is required which includes the interspecies extrapolation (10X) 

and intraspecies variability (10X) and the lack of data for neurotoxicity (acute and subchronic) 

and immunotoxicity (10X).
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A.4 Executive Summaries

A.4.1 Subchronic Toxicity

870.3100 90-Day Oral Toxicity- Rat

In a 90-day feeding study (MRID 00132689/47338506), groups of 20 male and female Wistar 

rats received diets containing 0, 50, 250, 1250 ppm paclobutrazol (91.9%) for 90 days. 

At 1250 ppm, increased liver weights and doubled the aminopyrene-N- demethylase activity was 

seen in the females. These effects were noted to a lesser extent in the females given diets 

containing 250 ppm, but without concomitant histological changes, the effects at the mid dose 

are unlikely to be toxicologically significant. Therefore, the NOEL for rats given paclobutrazol 

in the diet for 90 days is 250 ppm, and the lowest effect level (LEL) is 1250 ppm.

Based on additional data provided by the registrant (MRID 47338506, HED Document 011460), 

the actual doses used in the study were 0, 3.7, 18.8 or 93.0 mg/kg/day (M) and 0, 4.4, 21.6 or 

106.5 mg/kg/day (F). Accordingly, the NOAEL is 18.8 mg/kg/day (both sexes) and the LOAEL 

is 93.0 mg/kg/day, based on elevated liver weights, serum cholesterol, hepatic aminopyrene-Ndemethylase activity and alanine transaminase levels in females. 

The study is classified as Acceptable guideline. 

870.3200 21/28-Day Dermal Toxicity- Rabbit

In a 21-day dermal toxicity study (MRID 00132688), groups of 10 male and 10 female New 

Zealand white rabbits were treated with paclobutrazol at rates of 0, 10, 100, or 1000 mg per kg 

for 21 days. Twenty-four hours prior to the first application of the test substance, hair was 

clipped from the mid dorsal region of each rabbit. About 10% of each animal’s surface area was 

clipped; clipped treatment sites were abraded. The treatment sites on the remaining animals in 

each group were left intact. Hair clipping was repeated as needed during the 21-day treatment 

period, and abrasion was done on a weekly basis during the test. The test substance was 

suspended in 1% aqueous carboxymethyl cellulose and applied to the prepared skin sites 

bodyweight. After each application the treated areas were covered with an occlusive dressing for 

6 hours. At the end of that time the bandages were removed, and each test site was washed with 

warm tap water and blotted dry. This procedure was followed once each day 5 days each week 

for 3 consecutive weeks. During the study the animals were observed daily for the appearance of 

toxic signs, mortality, and behavioral changes. 

All dose levels (10, 100, or 1000 mg/kg/day) caused irritation of the abraded skin of test animals

but only the 100 and 1000 mg/kg/day doses irritated the intact skin sites of test animals. The 

irritation began to appear during the second week of dermal applications, and the degree of 

irritation increased with dose. Histologically, treated skin exhibited hyperkeratosis, acanthosis, 

and inflammatory changes of the superficial dermis. The NOAEL for intact skin with respect to 

these effects is 10 mg/kg/day, and the LOAEL is 100 mg/kg/day. The 1000 mg/kg/day dose 

(highest dose tested) caused severe irritation after two weeks of application to the skin of rabbits. 
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The study is classified as Acceptable/guideline

A.4.2 Prenatal Developmental Toxicity

870.3700a Prenatal Developmental Toxicity- Rat

In a developmental toxicity study (MRID 00132693), Paclobutrazol was tested in Wistar derived 

Alderley Park rats at the following dose levels: 0, 40, 100 or 250 mg/kg/day on days 6 - 15 of 

gestation. The NOAEL for maternal toxicity is 40 mg/kg/day and the LOEAL is 100 mg/kg/day. 

The effects were decrease in body weight gain (100 mg/kg/day and above), pallor and 

enlargement of the liver, decreased food consumption and food utilization, staining of the genital 

and ventral areas and mortality (250 mg/kg/day). The NOAEL for developmental toxicity is 40 

mg/kg/day (LDT) and the LOEAL is 100 mg/kg/day based on a dose-related increase in the 

incidence of delayed ossification at various sites and partial ossification of the odontal bone in 

the mid- and high dose groups and partial ossification of the occipital bone in the high dose 

group. The LOAEL is very close to 40 mg/kg/day because the increased incidence of delayed 

ossification was statistically significant for fetuses but not for litters. Cleft palate was also 

observed at dose levels that were maternally toxic. 

The study is reclassified as Acceptable/guideline

870.3700b Prenatal Developmental Toxicity- Rabbit

In a developmental toxicity study (MRID 407343020), Paclobutrazol was tested in New Zealand 

White rabbits at the following dose levels: 0, 25, 75 or 125 mg/kg/day. The maternal toxicity 

NOEL is 75 mg/kg/day and the maternal LEL is. 125 mg/kg/day based on decreases in body 

weights and body weight gain and food consumption during dosing. The developmental toxicity 

NOEL is 75 mg/kg/day and the LEL is 125 mg/kg/day based on the increased incidence of extra 

ribs in pups.

The study is reclassified as Acceptable/Guideline

A.5.3 Reproduction and Fertility Toxicity

870.3800 Reproduction and Fertility Effects – Rat

In a multigenerational reproduction study (MRIDs 40734303, 47338506), paclobutrazol 

(technical, 92.4%) was tested in Alpk:AP (Wistar derived) rats at the following dose levels: 0, 

50, 250 and 1250 ppm (o, 2.5, 12.5 or 62.5 mg/kg/day) in the diet. Each generation began with 

17 males and 34 females for each control and high does group and 15 males and 30 females for 

each low and mid-dose group. One male was mated with 2 females for m the same test group 

until sperm plugs were observed in vaginal smears. The F0 parental animals were given test diets 

for 12 weeks before they were mated, and the F1 parental animals were not mated until 11 weeks 

after they were selected from the F1A litters. Selection of parents for the F1 generation was made 

when the pups were 36 days of age, and the mated animals in the study were between 16 and 20 

weeks of age at mating. 
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At 250 ppm and above, an increased incidence of chromodacryorrhea and thickened

eyelids was observed in both generations. This was observed in both the prenatal

animals and in the pups. In the parental animals, the incidences were within the historical

control range. At 1250 ppm, increase I liver weights were observed in females in both 

generations (23% absolute, 26% relative F0; 7% absolute, 14% relative F1) and fatty change in 

the liver was observed in F0 females (23/30 versus 0/30 for the controls). Increased liver 

weights, mottling or accentuation of the lobular structure, liver enlargement and pallor and 

discoloration were observed in male and female pups from both generations. In addition to the 

changes in the liver, dental malocclusion was observed in both generations (parental animals and 

pups, incidence in the parental animals was within the historical control range) and thickening of 

the urinary bladder wall was observed in 1 F0 and in 3 F1 high dose females. The 

reproductive/systemic LOEL is 250 ppm (12.5 mg/kg/day) based on increased liver weights and 

on fatty change in the liver of parental females; and on an increased incidence of 

chromodacryorrhea and thickened eyelids, dental malocclusion, increased liver mottling or 

accentuation of the lobular structure, liver enlargement and pallor and discoloration in male and 

female pups. The reproductive/systemic NOEL is 50 ppm (2.5 mg/kg/day). This study is 

classified Acceptable/Guideline, and it satisfies the guideline requirement (870.7600) for a 

dermal penetration study.

Based on new information provided by the registrant (MRID 47338506) and HED’s analysis of 

individual data and historical control data on chromodacryorrhea and thickened eyelids, and 

dental malocclusion and twisted snouts and data on achieved doses for this study, the following 

changes have been made:

 NOELs and LOELs have been changed to NOAELs and LOAELs

The parental NOAEL for the two-generation reproduction study should be 250 ppm 

(equivalent to 23.2 mg/kg/day), and the LOAEL should be 1250 ppm (equivalent to 116.9 

mg/kg/day; the highest dose tested), based on increases in liver weight and fatty changes and 

thickening of the urinary bladder wall in the females. 

The reproductive NOAEL is 1250 ppm (equivalent to 116.9 mg/kg/day). 

The offspring NOAEL and LOAEL should be 250 ppm (equivalent to 23.2 mg/kg/day), and 

the LOAEL should be 1250 ppm (equivalent to 116.9 mg/kg/day), based on the increased 

incidence of dental malocclusions, chromodacryorrhea and thickened eyelids; increased liver 

weights, mottling or accentuation of the lobular structure of the liver, along with liver 

enlargement, pallor and discoloration.

For more details see TXR 0056158

A.4.4 Chronic Toxicity

870.4100a Chronic Toxicity – Rat 

In a combined chronic feeding/oncogenicity study (MRIDs 40734301, 47078901) SpragueDawley Crl:CD(SD)BR rats. Fifty animals/dose/sex were fed 0, 50, 250 or 1250 ppm technical 

Paclobutrazol (92.4% pure) in the diet (0, 2.5, 12.5 or 62.5 mg/kg/day) for 2 years. An additional 
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ten animals/sex were placed in the control and high dose groups as microbiological sentinels. 

Another 10 animals/sex were added that were sacrificed at 52 weeks.

At 62.5 mg/kg/day, there was an increase in hypertrophy/steatosis of the liver (both sexes) and 

increased liver weights (14 and 13% in males and 9 and 24% in females for absolute and relative 

liver weights over control values, respectively). The LOEL is 1250 ppm (62.5 mg/kg/day) based 

upon an increase in hypertrophy/steatosis of the liver (both sexes). The NOEL for chronic effects 

is 250 ppm (12.5 mg/kg/day).

There appeared to be a borderline increase in uterine stromal polyps in the high dose and 

possibly mid—dose females (0/50, 4/50, 5/50 and 7/50 for the control, low dose, mid—dose and 

high dose groups, respectively). Pairwise comparisons were statistically significant at all dose 

levels (p<0.05, p<0.0l and p<0.Ol for the low dose, mid-dose and high dose groups, 

respectively), and a positive trend was observed with increasing dose (p<0.O5). Although the 

authors stated that this was due to the 0 frequency in the controls, which is unusual, it is 

considered to be a possible positive response. However, the study is considered to be inadequate 

for classification of the chemical for carcinogenicity for the following reason: although the 

chronic effects are considered to be sufficient to establish a NOEL and an LEL for chronic 

toxicity, they are not considered to be severe enough to indicate that the animals were tested at a 

sufficiently high dose level for an adequate oncogenicity study.

This study is classified as Core Minimum as a chronic feeding study and Core Supplementary as 

oncogenicity study. It does not satisfy the regulatory requirement for an oncogenicity study. Due 

to the low dose levels tested and to the possible positive response for uterine stromal polyps, a 

repeat study will be needed if the use pattern for the chemical requires it.

870.4100b Chronic Toxicity – Dog 

In a one-year chronic toxicity study (MRID 00132691/00143166), groups of four groups of six 

male and female beagles received daily doses of paclobutrazol (92.4%) at 0, 15, 75 and 300 

mg/kg/day for 1 year. Doses were administered in capsules. 

Elevated serum alkaline phosphatase and triglyceride levels, the enlarged hepatic cells, increased 

liver weights, and increased hepatic aminopyrine N-demethy- lase activity indicate that the two 

highest doses (75 and 300 mg/kg/day) have definite effects. However, no toxicologically 

significant effects were observed at the .15 mg/kg/day dose level. The NOEL is 15 mg/kg/day, 

and the LEL is 75 mg/kg/day in beagle dogs.

This study is classified as Core Minimum.

A.4.5 Carcinogenicity

870.4200a Carcinogenicity - Rat

See MRID 40734301
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870.4200b Carcinogenicity – Mouse

In a combined chronic feeding/oncogenicity study (MRID 402762501) in Crl:CD- l (ICR)BR 

albino mice. Fifty-one animals/sex/group were fed 0, 25, 125 or 750 ppm technical 

Paclobutrazol (92.4% pure) in the diet for 2 years (0, 3.75, 18.75 or 112.5 mg/kg/day). Two 

control groups of 51 animals/sex were utilized. Nine additional animals/sex in the first control 

and high dose groups were kept as microbiological sentinels.

At 112.5 mg/kg/day, there was an increase in the severity of steatosis of the liver (males). There 

were also minor increases in relative and absolute liver weights (21% greater than controls for 

both absolute and relative, liver weights in sales and 18 and 19% greater than controls for 

absolute and relative liver weights, respectively for females) the LOEL is 750 ppm (112.5 

mg/kg/day) based on increases in severity of steatosis of the liver in males. The NOEL for 

chronic effects is 125 ppm (18.85 mg/kg/day).

There appeared to be a borderline increase in Leydig cell tumors in high dose males (2/53, 0/50, 

2/51, 1/52 and 5/52 for the control 1, control 2, low, mid- and high-dose groups, respectively). A 

pairwise comparison was statistically significant at the highest dose level (p<0.05)*. In addition, 

a positive trend was observed with increasing dose (pcO.O5). Although the authors stated that 

this was not considered to be biologically significant because the control values were low, it is 

considered to be a possible positive response. However, the study is considered to be inadequate 

for classification of the chemical for carcinogenicity for the following reason: although the 

chronic effects are considered to be sufficient to establish a NOEL and an LEL for chronic 

toxicity, they are not considered to be severe enough to indicate that the animals were tested at a 

sufficiently high dose level for an adequate carcinogenicity study.

This study is classified as core Minimum as a chronic feeding study and Core Supplementary as 

oncogenicity study (see discussion). It does not satisfy the regulatory requirement for an 

oncogenicity study. Due to the low dose levels tested and to the possible positive response for 

Leydig cell tumors, a repeat study will be needed if the use pattern for the chemical requires it.

A.4.6 Mutagenicity

Gene Mutation

Guideline 870.5100 Bacterial reverse mutations 

(Ames assay)

MRID 00017480

Classification: Acceptable/guideline

Paclobutrazol was negative for the induction of 

reverse gene mutations in Salmonella typhimurium

TA1535, TA1537, TA1538, TA98, and TA100 at 

concentrations of 0, 1.6, 8.0, 40, 200, 500, 1000, 

2500 or 5000 μg/plate +/-S9 activation. 

Cytotoxicity and compound precipitation was 

reported at 5000 μg/plate.

Guideline 870.5300 In vitro mammalian cell gene 

mutation (mouse lymphoma L5178Y cells) 

MRID 00132695

Classification: Acceptable/guideline

Paclobutrazol was negative for the induction of 

forward gene mutations in mouse lymphoma 

L5178Y cells at the TK locus at concentrations 0, 

0.1, 12.0, 10.3, and 102.5 μg/mL +/-S9. Severe 

cytotoxicity (≤6% cell survival) was seen at 102.5 

μg/mL +/-S9
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In Vivo Chromosomal Aberrations

Guideline 870.53.75 In vivo bone marrow 

chromosome aberration (Rat)

MRID 00143156

Classification: Acceptable/guideline

Paclobutrazol was negative for the induction of 

chromosome aberrations in the bone marrow of 

Alderly Park male and female rats at doses of 0, 30, 

150, or 300 mg/kg/day, once daily for 5 consecutive 

days via oral gavage. 

Guideline 870.5300 Mouse Micronucleus Assay 

MRID 00132694

Classification: Acceptable/guideline

Paclobutrazol was negative for the induction of 

micronucleated polychromatic erythrocytes in the 

bone marrow of mice at 0, 87.5 or 140 mg/kg. The 

doses represent 50 and 80%, respectively of the 

LD50 when delivered via intrapertioneal injection. 

Guideline 870.5450 Rodent Dominant Lethal Test 

(Mouse) MRID 00143155

Classification: Acceptable/guideline

Paclobutrazol was negative for the induction of 

dominant lethal mutations in the spermatocytes of 

CD-1 mice administered 0, 30, 150 or 300 

mg/kg/day, once daily for 5 consecutive days via 

oral gavage. 

Other In Vivo Studies 

Guideline 870.550 In vivo Unscheduled DNA 

Synthesis assay ( UDS, rat hepatocytes)

MRID 00017480

Classification: Acceptable/guideline

Paclobutrazol was negative for the induction of 

UDS in hepatocytes harvested from Alderly Park 

rats treated with 0, 40, or 400 mg/kg of the test 

material. 

A.4.7 Neurotoxicity

870.6200 Acute Neurotoxicity Screening Battery – data gap

870.6200 Subchronic Neurotoxicity Screening Battery – data gap

870.6300 Developmental Neurotoxicity Study – not required at this time

A.4.8 Metabolism 

870.7485 Metabolism – Rat

In a metabolism study (MRID 00132696), male and female Wistar rats received a single oral 

gavage dose of 10 mg/kg of paclobutrazol (99%) or 10 mg/kg paclobutrazol radiolabeled with 

14C on the triazole ring for 4 days. Single rats/sex were subjected to autoradiography 24 hours 

after dosing and 3 rats per sex were sacrificed 72 hours after dosing and autoradiography, Urine, 

feces, cage washings and tissues (adipose tissue, gonads, kidneys, and liver were analyzed. 

During the 4 days following administration, 39.18 and 52.6 % of the dose was recovered in the 

urine of male and female rats, respectively. Fecal recoveries were 53.49% in the males and 37% 

in females. Approximately 60% of the administered dose was accounted for in feces and urine 

of males and females during the first 24 hours of dosing. Residue concentrations in tissues 3 or 
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4 days after dosing did not indicate accumulation, and urinary excretion along with slow fecal 

excretion indicated a significant gastrointestinal absorption of the dose. 

The study is Acceptable/guideline. 

In a metabolism study (MRID 00143160), 1 male and 1 female rat received a single oral gavage 

dose of 250 mg/kg of paclobutrazol (99%) mixed with radiolabeled paclobutrazol (specific 

activity = 1.68 GBq/mM 32.16 μCi/mg) for 48 hours. Urine, feces and expired air samples were 

collected for analysis at 24 and 48 hours. Animals were sacrificed at 48 hours and subjected to 

autoradiography. 

Autoradiographs indicated that the liver, kidneys, and gastrointestinal tract contained the 

administered radiolabel. Similarly, the disposition of the 14c label after a single oral dose of 250 

mg/kg is limited to the gastrointestinal contents and to a lesser extent to the liver and kidneys. 

The study is Acceptable 

In a metabolism study (MRID 00143161), 4 male and 4 female Wistar rats received a single oral 

gavage dose of 5 mg/kg of paclobutrazol (99%) or 5 mg/kg paclobutrazol radiolabeled (specific 

activity = 32.16 μCi/mg) for 7 days. Urine and feces samples were collected for analysis at 24 

hour intervals for 7 days. Animals were sacrificed at 7 days post-treatment and organ samples 

were taken.

Most of the 5 mg/kg dose was excreted within 72 hours (70-80%). Approximately 55% of the 

dose was recovered in the urine of both sexes, and 32% or 24% was recovered in the feces of 

males and females, respectively. 7 days after dosing, liver tissue contained 0.017 to 0.028 ppm; 

gastrointestinal tract contained 0.012-0.025 ppm. No other tissue levels were detectable. 

The study is Acceptable/guideline. 

In a metabolism study (MRID 00143165), male and female rats received a single oral gavage 

dose of 5 or 250 mg/kg of radiolabeled paclobutrazol (specific activity = 1.68 GBq/mM 32.16 

μCi/mg) for 3 days. The animals were placed in metabolism cages and urine and feces samples 

were collected for analysis at 24-hour intervals for 3 days. A second series of animals (2 males 

and 2 females) were cannulated and given 250 mg/kg paclobutrazol by oral gavage. Urine, bile 

and feces samples were collected for analysis at 24-hour intervals for 4 days. Animals were 

sacrificed at the end of the treatment time subjected to autoradiography. 

A single oral gavage dose (5 or 250 mg/kg) paclobutrazol was absorbed almost completely by 

male and female rats. Triazole and halogenated phenyl moieties not affected in rat. Pentanol 

moiety oxidized to a diol or carboxylic acid & excreted in free or conjugated forms. Males 

excreted more of carboxylic acid metabolites than females but proportion of acid metabolites 

excreted by females increased as dose decreased. Approx. 75% of dose was recovered in bile 

during first 48 hours after dosing in males, and 50% is recovered from females during first 72 

hours.
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The study is Acceptable. 

870.7485 Metabolism – Dog

In a metabolism study (MRID 00143163) in dogs, three male and three female beagle dogs were 

given single oral doses of 5mg//kg radiolabeled (specific activity = 32.16 μCi/mg) and unlabeled 

paclobutrazol. Blood samples were drawn prior to dosing, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24,48, 72, 

96, 120, 144, and 168 hours after treatment. Urine and feces samples were collected for analysis 

at 24 hour intervals for 7 days. Animals were sacrificed at 7 days pot-treatment and organ 

samples were taken.

Paclobutrazol was rapidly absorbed in the dog after a single oral dose of 5 mg/kg is 

administered. Peak plasma and blood levels were observed 1.5 hours after dosing. During the 

24 hours following dosing, approximately 80-85% of 5 mg/kg dose extracted during first 24 

hours after dosing. Approx. 50% of dose recovered in urine of both sexes, & 35-40% recovered 

in feces. Peak blood levels at 1 hour after dosing (4.1-4.4 ppm in plasma) declined to pre-dose 

levels 24-48 hours after treatment. No detectable levels in tissue & no sex differences were 

observed. 

The study was classified as Acceptable/guideline

A.4.9 Dermal penetration 

870.7600 Dermal penetration – Rat

In an in vivo percutaneous absorption study (MRID 41048202), groups of five male rats 

(5/dose/exposure period) were dosed dermally on an area of 10 cm2per rat with 0.011, 0.025, 

0.125, 1.23, or 12.49 mg/rat paclobutrazol for 10 or 24 hours. The percentage of dose absorbed 

and remaining on the washed application site, for exposures of 10 and 24 hours are as follows: 

Dose

mg/rat

Total Absorbed (%) Application Site

10 hrs 24 hrs 10 hrs 24 hrs

12.49 1.12 2.78 2.57 2.4

1.23 3.3 3.2 1.6 0.8

0.125 11.6 10.4 0.8 1.6

0.025 16.0 20.8 2.4 2.4

0.011 15.1 24.5 3.6 2.7

 

This study is classified Acceptable/Guideline, and it satisfies the guideline requirement 

(870.7600) for a dermal penetration study.
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Appendix B: Review of Human Research

This risk assessment relies in part on data from studies in which adult human subjects were 

intentionally exposed to a pesticide or other chemical. These studies, which comprise the 

Pesticide Handlers Exposure Database (PHED), the Outdoor Residential Exposure Task Force 

(ORETF) Database, the Agricultural Handler Exposure Task Force (AHETF), Agricultural 

Reentry Task Force (ARTF), and a number of studies utilized in the 2012 Lawn/Turf SOP have 

been determined to require a review of their ethical conduct, have received that review, and have 

been determined to be ethically conducted.
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Appendix C: Physical and Chemical Properties

Appendix Table C.1: Paclobutrazol Physical and Chemical Properties

Parameter Value

Molecular Weight 293.8 g/mol

Water solubility (20°C) 25.9 mg/L (water)

Solvent solubility (20°C)

2.8 g /L (n-Octanol)

79.8 g/L (methanol)

5.22 g/L (xylene)

Vapor pressure (20°C) 1.28 x 10-9 mmHg

Henry’s Law Constant (25°C) 8.2 x 10-7 Pa M3 mol-1

(8.09 x 10-12 atm M3 mol-1)

Octanol/water partition coefficient (25°C) log Kow = 3.18