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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460

 OFFICE OF 

 CHEMICAL SAFETY AND 

POLUTION PREVENTION

MEMORANDUM

Date: July 28, 2010 

SUBJECT: Propiconazole: Section 18 Emergency Exemption for Propiconazole (Tilt® EPA Reg. No. 100-

617); for Use on Avocado Trees. 

PC Code: 122101 DP Barcode: D380160 

Decision No.: 436555 Registration No.: 100-617 

Petition No.: N/A Regulatory Action: Section 18 

Risk Assessment Type: Single Chemical Aggregate CAS No.: 3125

TXR No.: NA 40 CFR: 180.434

MRID No.: None 

FROM: James S Miller, Environmental Scientist 

 Risk Assessment Branch IV 

 Health Effects Division (7509P) 

 Office of Pesticide Programs 

THRU: Raymond Kent, Chief, 

 Risk Assessment Branch IV 

 Health Effects Division (7509P) 

 Office of Pesticide Programs 

TO: Bonnie Cropp-Kohlligian, Risk Assessor 

A. Conrath /B. Madden RM 05 

 Risk Integration, Minor Use, and Emergency Response Branch 

 Registration Division (7505P) 

 Office of Pesticide Programs 

Introduction 

In a memorandum dated June 17, 2010, the Florida Department of Agriculture and Consumer 

Services submitted a request for the use of (Tilt®) propiconazole, to manage Laurel Wilt 

(Raffaelea lauricola) on avocados. This action was requested due to the fact that the redbay 

ambrosia beetle (Xykebirusu plabratus) is a non-native insect that was identified for the first time 

in the United States in Georgia in 2002. Laurel Wilt has a symbiotic relationship with the redbay 

ambrosia beetle. In a combined effort between state and federal agencies, it has been determined 

that avocado trees are very susceptible to this disease and that there are no existing registered 

pesticides that can adequately protect avocados. In January of 2010, a redbay beetle was 
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discovered near a main avocado production area in Miami-Dade County. Florida has 

approximately 7,500 acres of commercially grown avocados, most of which are grown in MiamiDade County. 

Propiconazole, [[2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-2-yl]methyl]-1H-1,2,4-triazole 

is a systemic triazole fungicide with protective and curative action. Propiconazole is formulated 

as liquids (emulsifiable, soluble, and flowable concentrates packaged as “mix-your-own” and 

“ready-to-use” (RTU) products) and wettable powders in water-soluble packets (WP/WSP). 

Application rates vary depending upon the application equipment and crop or use-site. 

Currently, propiconazole is registered for use in a variety of occupational and residential sites. 

Occupational uses include conventional agricultural and commercial sites, as well as 

antimicrobial uses. Residential use-sites include ornamentals (herbaceous, woody, non-bearing 

fruit/nut trees), turf (lawn applications), and garden crops with applications being performed by 

both professionals and homeowners. 

 For the purpose of this registration action, three general application methods are being considered and 

assessed for the use propiconazole as an emulsifiable concentrate (Tilt® EPA Reg. No. 100-617) on 

Avocado Trees. Soil Application, which is designed to be absorbed by the roots and distributed in the 

xylem throughout the tree, a tree directed application with a handgun focusing on applying the product to 

the bark surfaces of all ages of tree, and tree injection through the trunk of the tree and distributed in the 

xylem throughout the tree. As noted within, this document only addresses exposures and risks for 

commercial agricultural uses, residential, and antimicrobial uses will not be addressed.

1.0 Hazard Characterization 

On February 13, 2003 the Health Effects Division (HED) Hazard Identification Assessment 

Review Committee (HIARC) reassessed FQPA requirements (TXR 0052277) for 

propiconazole in response to questions posed by the Natural Resources Defense Council 

(NRDC). No new data have been reviewed and no changes were made to the toxicology 

endpoints previously selected for Propiconazole (TXR 0050439 & 0051703). In October, 

2005, the registrant conducted an ACN study (MRID 46604601) with propiconazole and 

submitted it to the Agency. Evaluation of this ACN study demonstrated that severe clinical 

signs of toxicity were not accompanied by nervous tissue damage and neurobehavioral effects 

were minimal. The propiconazole risk assessment team concluded that the ACN study satisfies 

the data gap imposed by HIARC and the 3X factor for the data base uncertainty factor (UFDB) 

can be reduced to 1X. The rat acute study also serves as the basis for short-term dermal and 

inhalation scenarios.
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1.1 Acute Toxicological Categories 

Table 1: Propiconazole Acute Toxicity Profile 

Guideline 

No. Study Type MRID # Results Toxicity Category

870.1100 Acute Oral - rat 00058591 LD50 =1517 mg/kg III 

870.1200 Acute Dermal-rabbit 00058596 LD50 = >4000 mg/kg III 

870.1300 Acute Inhalation - rat 41594801 LC50 = >50.84 mg/L IV 

870.2400 Primary Eye Irritation 00058597 Corneal opacity reversed 

in 72 hours III 

870.2500 Primary Skin Irritation 00058598 No irritation IV 

870.2800 Dermal Sensitization 44949501 Non sensitizer - 

1.2 Toxicological Endpoints 

Dermal Endpoints: 

The short-term endpoint selected was based on acute clinical toxicity observed in the acute 

neurotoxicity study in rats (ACN) (MRID 46604601) discussed above. It was concluded that 

the LOAEL for the clinical signs of toxicity in this ACN study was 100 mg/kg and the 

NOAEL was 30 mg/kg. This endpoint is appropriate since the severe clinical effects were 

observed after administration of the test material within one day. Since an oral dose was 

selected, a 40% dermal absorption factor is used for route to route extrapolation. 

Furthermore, due to the use pattern of this registration action, HED has determined that only a 

short-term assessment is appropriate, therefore and intermediate-, and long-term assessments 

were not conducted. 

Inhalation Endpoints: 

The short-term inhalation toxicological endpoint is 30 mg/kg/day based on an acute rat acute 

neurotoxicity study (MRID 46604601). An inhalation absorption factor of 100% (default value 

assuming equivalent inhalation and oral absorption) will be used for route-to-route 

extrapolation. Since the short-term and intermediate-/long-term dermal and inhalation 

toxicological endpoints of concern are the same, respectively for each duration, and based on 

oral studies, assessments of each exposure duration combines the dermal and inhalation doses 

and applies the appropriate route-specific absorption factor explained above. 
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However, due to the use pattern of this registration action, HED has determined that only a 

short-term assessment is appropriate, therefore and intermediate-, and long-term assessments 

were not conducted. 

The Agency’s level of concern for non-cancer risks (i.e., target level for MOEs or Margins of 

Exposure) is defined by the uncertainty factors that are applied to the assessment. The Agency 

applies a 10X factor to account for inter-species extrapolation and a 10X factor to account for 

intra-species sensitivity. The total uncertainty factors that have been applied to non-cancer risk 

assessments are 100 for occupational, 100 for short-term residential and 100 for intermediate-, 

long-term residential scenarios (based on the toxicology endpoint selection for General 

Population including infants and children. 

Propiconazole is listed as a Group C, Possible Human Carcinogen. A Q1* was not identified 

for propiconazole, therefore a quantitative cancer risk assessment is not required.

A margin of exposure (MOE) of 100 defines HED’s level of concern (LOC) for commercial 

agricultural (occupational) exposures. 

Table 2: Propiconazole Toxicological Endpoints 

Exposure 

Scenario

Dose Used in Risk 

Assessment, UF

Special FQPA SF* and 

Level of Concern for Risk 

Assessment

Study and Toxicological 

Effects

Short-Term 

(1-30 days) 

Incidental Oral

NOAEL= 30 mg 

ai/kg/day 

Residential MOE = 100

Occupational = NA 

Acute Neurotoxicity Study-Rats 

Clinical signs (piloerection, 

diarrhea, tiptoe gait). 

Intermediate-Term 

(1 - 6 months) 

Incidental Oral

NOAEL= 10 mg 

ai/kg/day 

Residential MOE = 100

Occupational = NA 

24 Month Oncogenicity Study - 

Mice. 

Liver toxicity (increased liver 

weight in males and increase in 

liver lesions (masses/raised 

areas/ swellings/nodular areas 

mainly) 

Short-Term

(1 - 30 days) Dermal

(General Population, 

including infants and 

children) 

Oral Maternal NOAEL= 

30 mg ai/kg/day 

Dermal absorption 

(Rate = 40%) 

Residential MOE = 100

Occupational MOE = 100

Acute Neurotoxicity Study-Rats 

Clinical signs (piloerection, 

diarrhea, tiptoe gait). 

Intermediate-Term 

(1 - 6 months) and 

Long-Term Dermal

(>6 months) 

Oral NOAEL= 10 mg 

ai/kg/day 

Dermal absorption 

(Rate = 40%) 

Residential MOE = 100

Occupational MOE = 100

24 Month Oncogenicity Study - 

Mice. 

Liver toxicity (increased liver 

weight in males and increase in 

liver lesions (masses/raised areas/ 

swellings/nodular areas mainly) 
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Table 2: Propiconazole Toxicological Endpoints 

Exposure 

Scenario

Dose Used in Risk 

Assessment, UF

Special FQPA SF* and 

Level of Concern for Risk 

Assessment

Study and Toxicological 

Effects

Short-Term

(1 - 30 days) 

Inhalation

Oral Dev. NOAEL= 

30 mg/kg/day 

Inhalation absorption 

(Rate = 100%) 

Residential MOE = 100

Occupational MOE = 100

Acute Neurotoxicity Study-Rats 

Clinical signs (piloerection, 

diarrhea, tiptoe gait 

Intermediate-Term 

(1 - 6 months)

Long-Term Inhalation

(>6 months) 

Oral NOAEL= 

10 mg/kg/day 

Inhalation absorption 

(Rate = 100%) 

Residential MOE = 100

Occupational MOE = 100

24 Month Oncogenicity Study - 

Mice. 

Liver toxicity (increased liver 

weight in males and increase in 

liver lesions (masses/raised areas/ 

swellings/nodular areas mainly) 

Cancer

(Oral, dermal, 

inhalation) 

Group C, possible human carcinogen, RfD approach for risk characterization. 

2.0 Occupational Handler and Post-application Exposure and Risk 

Occupational handler exposure is expected for certified applicators applying propiconazole to 

avocado trees. Handler risks were assessed using a (Surrogate Exposures Guide) from the 

Pesticide Handlers Exposure Database (PHED). The occupational handler scenarios resulted in 

MOEs that do not exceed HED's level of concern (i.e., MOEs > 100) while adhering to label 

specific PPE directions, (i.e., Long Sleeve Shirt, Long Pants, Socks, Shoes, and Chemical 

Resistant Gloves). 

Chemical-specific data were not submitted to the Agency in support of this Section 18 

application, therefore it is HED policy to use data from the Pesticide Handlers Exposure 

Database (PHED) Version 1.1 (Surrogate Exposures Guide) to assess handler exposures in the 

absence of chemical specific data. According to the propiconazole label; (Tilt® EPA Reg. No. 

100-617) relevant exposure scenarios for occupational handlers are (1) application via handgun 

sprayer, (2) application via tree injection, and (3) application via soil drenching equipment 

(Groundboom). The unit exposure values provided in the PHED (Surrogate Exposures Guide) 

were used for exposure, dose and MOE (Margin of Exposure), calculations. 

The average adult weight of 60 kg was used for estimating dermal and inhalation exposure. 

Furthermore, the use patterns presented on the proposed label are expected to result in short-term 

(1-30 days) exposure only. For all occupational handlers exposure scenarios, risks are below 

HED’s level of concern (i.e., MOEs are > 100) with label specific PPE and therefore not of 

concern. 
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Label specific directions state that the Personal Protection Equipment (PPE) required for this 

action falls under category G, (long-sleeved shirt, long pants, chemical resistant gloves, shoes 

plus socks, and protective eyewear). Furthermore the restricted entry interval (REI) is 12 hours, 

unless soil injected, which under the WPS (worker protection Standards) allows workers to reenter treated areas if there will be no contact with treated materials. 

Note: Based on the use pattern (soil directed/tree bark) associated with the proposed Section 18 

label, HED believes that post-application exposure will be negligible. Therefore, a postapplication quantitative assessment was not conducted. 

The resulting doses and MOEs are presented in Table 3. 
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Table 3: Short-Term Occupational Handler Exposure and Risk for Propiconazole (Tilt® EPA Reg. No. 100-617) 

Exposure 

Scenario Crop App Rate (lb ai/A)a

Acres 

Treated 

Daily 

Unit Exposure (mg/lb ai)b Dose (mg/kg/Day) Short-Term 

MOEs 

Dermal 

Long Sleeve 

Shirt, Long 

Pants + Gloves 

Baseline 

inhalation 

 Dermal 

Long Sleeve 

Shirt, Long 

Pants + Gloves 

Baseline 

Inhalation 

Combined 

MOEc

Open Mixer/Loader (Liquid) 

1

Handgun 

Sprayer (PHED) 

Avocado 

Trees 7.1 100 0.023 1.2 0.10886 0.0142 240 

Applying (Liquid) 

1

Handgun 

Sprayer (PHED)

Avocado 

Trees 7.1 5 0.34 1.4 0.08046 0.00008 370 

Mixer/Loader/Applicator (Liquid) 

2

Groundboom 

Soil Drench 

(PHED)

Avocado 

Trees 7.1 80 0.057 1.3 0.21584 0.01231 130 

Applicator (Liquid) 

2

Groundboom 

Soil Drench 

(PHED)

Avocado 

Trees 7.1 80 0.014 0.74 0.05301 0.00701 500 

Applicator 

Tree Injection Not Assessed: Handgun and Soil Drench are protective 

1Handgun Sprayer (PHED) acrea treated based on HED directions: 100 Acres mixed = 20 workers x 5 Acres. (Individual worker mixes = 100 Acres / day) 2

Soil Drench calculations Groundboom: 80 Acres / day . PHED SOP.009 

a. Application rate based on proposed uses on the label for (Tilt® EPA Reg. No. 100-617) 

b. Unit Exposures based on PHED Version 1.1. Surrogate Exposures Guide. 

C. Combined MOE = inhalation + Dermal 
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3.0 Residential Handler and Post-application Exposure and Risk 

Due to the nature of this registration action, a residential handler and post-application assessment 

were not conducted. 

Spray Drift

Spray drift is always a potential source of exposure to residents nearby to spraying operations. 

This is particularly the case with aerial application, but, to a lesser extent, could also be a 

potential source of exposure from the ground application method employed for propiconazole. 

The Agency has been working with the Spray Drift Task Force, EPA Regional Offices, and State 

Lead Agencies for pesticide regulation and other parties to develop the best spray drift 

management practices. The Agency is now requiring interim mitigation measures for aerial 

applications that must be placed on product labels/labeling. The Agency has completed its 

evaluation of the new data base submitted by the Spray Drift Task Force, a membership of U.S. 

pesticide registrants, and is developing a policy on how to appropriately apply the data and the 

AgDRIFT computer model to its risk assessments for pesticides applied by air, orchard airblast, 

and ground hydraulic methods. After the policy is in place, the Agency may impose further 

refinements in spray drift management practices to reduce off-target drift and risks associated 

with aerial as well as other application types where appropriate. Note that in this assessment, 

propiconazole is not directly applied to residential turf and does not result in exposures of 

concern. It is unlikely that spray drift would result in a higher potential for risk of exposure than 

the scenarios already assessed. 

4.0 Conclusion 

For all occupational application exposure scenarios, Margins of Exposure (MOEs) were ≥100 

and therefore risks were not observed at the enclosed application rate. Furthermore, 

Propiconazole is listed as a Group C, Possible Human Carcinogen. A Q1* was not identified 

for propiconazole, therefore a quantitative cancer risk assessment is not required.