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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

 OFFICE OF CHEMICAL SAFETY 

 AND POLLUTION PREVENTION 

 

MEMORANDUM

Date: July 29, 2010 

SUBJECT: Propiconazole. ID#10FL02 Section 18 Emergency Exemption for the Use of 

Propiconazole on Avocado Trees in Commercial Orchards of Florida to Control 

Laurel Wilt. 

PC Code: 122101 DP Barcode: D379849 

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

Petition No.: None Regulatory Action: Section 18 

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

TXR No.: N/A CAS No.: 60207-90-1

MRID No.: N/A 40 CFR: § 180.434

FROM: Bonnie Cropp-Kohlligian, Environmental Scientist/Risk Assessor 

 Risk Assessment Branch 4 

Health Effects Division (7509P)

THROUGH: Susan Hummel, Chemist/ Senior Scientist 

Risk Assessment Branch 4 

Health Effects Division (7509P) 

TO: Andrea Conrath/Barbara Madden, RM#5 

 Risk Integration, Minor Use and Emergency Response Branch 

 Registration Division (7505P) 

The Registration Division (RD) of the Office of Pesticide Programs (OPP) has requested that the 

Health Effects Division (HED) evaluate the Section 18 Emergency Exemption request 

(ID#10FL02) for the first time use of the fungicide propiconazole to control laurel wilt on 

avocado trees in commercial orchards of Florida; potentially treating up to 7,500 acres. The 

product to be used is Tilt® Fungicide (EPA Reg. No. 100-617), a 3.6 lb/gal emulsifiable 

concentrate (EC) formulation containing 41.8% propiconazole by weight. 

Attached is the HED human health risk assessment of propiconazole for the purposes of issuing 

the subject Section 18 Emergency Use for this active ingredient. There are registered 

antimicrobial uses for propiconazole as well and the Antimicrobial Division (AD) has conducted 
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a risk assessment for all existing and potential antimicrobial uses. The present aggregate risk 

assessment includes the risks from antimicrobial uses in mushroom houses (dietary) and in 

treated wood in play sets and residential decks (residential postapplication exposure). 

Propiconazole is among the group of chemicals which generate the common triazole metabolites, 

1,2,4-triazole and its conjugates triazolylalanine, triazolylacetic acid and triazolylpyruvic acid. 

Issues concerning propiconazole and the common triazole metabolites have been addressed 

under a separate heading in the Executive Summary only. 

Supporting documents completed for the subject Section 18 Registration are listed below: 

 1) Section 18 Drinking Water Assessment; EFED memo by J. Lin (D379850, 7 /15/10). 

2) Section 18 Propiconazole Dietary Exposure and Risk Assessment; HED memo by T. 

Morton (D380158, 7/21/10). 

3) Section 18 Common Triazole Metabolites Updated Dietary Exposure and Risk 

Assessment; HED memo by T. Morton (D380341, 7/27/10). 

4) Section 18 Occupational and Residential Exposure Assessment; HED memo J. Miller 

(D380160, 7/28/10). 

 
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TABLE OF CONTENTS 

 pg. 

1.0 EXECUTIVE SUMMARY .................................................................................................4 

2.0 INGREDIENT PROFILE ....................................................................................................9 

2.1 Proposed New Uses .............................................................................................................9 

2.2 Structure and Nomenclature .............................................................................................11

2.3 Physical and Chemical Properties ......................................................................................12 

3.0 HAZARD ASSESSMENT ...............................................................................................12 

3.1 Hazard Profile ...................................................................................................................12 

3.2 FQPA Hazard Considerations ...........................................................................................14 

3.3 Summary of Toxicity Endpoint Selection ..........................................................................14 

3.4 Endocrine Disruption .........................................................................................................16 

4.0 DIETARY EXPOSURE/RISK CHARACTERIZATION .................................................16 

4.1 Residue Chemistry Profile .................................................................................................16 

4.2 Drinking Water Profile ......................................................................................................18 

4.3 Dietary Exposure and Risk Assessment ............................................................................18 

5.0 RESIDENTIAL (NON-OCCUPATIONAL) EXPOSURE/RISK 

CHARACTERIZATION ...................................................................................................20 

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

5.2 Residential Postapplication Exposure and Risk Characterization .....................................22 

6.0 AGGREGATE RISK ASSESSMENTS and CHARACTERIZATION ............................25 

6.1 Acute and Chronic Aggregate Risk ...................................................................................25 

6.2 Short-Term Aggregate Risk ...............................................................................................25

6.3 Intermediate-Term Aggregate Risk ...................................................................................27 

6.4 Long-Term Aggregate Risk ...............................................................................................27 

7.0 CUMULATIVE RISK CHARACTERIZATION/ASSESSMENT ...................................28 

8.0 OCCUPATIONAL EXPOSURE and RISK ......................................................................29 

8.1 Occupational Handler Exposure and Risk .........................................................................29 

8.2 Occupational Postapplication Exposure and Risk .............................................................31 

9.0 REFERENCES ..................................................................................................................31 
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1.0 EXECUTIVE SUMMARY

Propiconazole is a triazole-derivative fungicide that provides broad spectrum disease control on a 

variety of crops. It is a member of the class of the ergosterol biosynthesis inhibiting fungicides. 

The mode of antifungal action of propiconazole is attributed to the inhibition of CYP51 

(lanosterol-14-a-demethylase). 

Tolerances are currently established for the combined residues of propiconazole, 1-[[2-(2,4-

dichlorophenyl)-4-propyl-1,3-dioxolan-2-yl]methyl]-1H-1,2,4-triazole, and its metabolites 

determined as 2,4-dichlorobenzoic acid (2,4-DCBA) and expressed as parent compound in 40 

CFR §180.434. Tolerances have been established for plant commodities in 40 CFR §180.434(a), 

at levels ranging from 0.1 ppm for several commodities to 40 ppm for grass straw. Tolerances 

for residues in livestock commodities are also established under 40 CFR §180.434(a), and range 

from 0.05 ppm for several commodities to 2.0 ppm for liver and kidney of cattle, goat, horse, and 

sheep; no tolerances in poultry and eggs have been established. Time-limited tolerances are 

established in 40 CFR §180.434(b) for nectarine and peach (expiration date of 12/31/10); 

tolerances with regional registration are established in 40 CFR §180.434(c) for cranberry and 

wild rice; and tolerances for indirect or inadvertent residues are established in 40 CFR 

§180.434(d) for alfalfa forage and hay. 

Proposed Uses

The Florida Department of Agriculture and Consumer Services has requested a Section 18 

Emergency Exemption (ID#10FL02) to use propiconazole to control laurel wilt on avocado trees 

in commercial orchards of Florida, most of which are in the Miami-Dade County area. The 

product to be used is Tilt® Fungicide (EPA Reg. No. 100-617), a 3.6 lb/gal emulsifiable 

concentrate (EC) formulation containing 41.8% propiconazole by weight. The proposed 

emergency use does not include homeowner use or application to residential areas. 

Application methods include: (1) soil drench (groundboom), (2) tree-directed (hand-held spray 

gun/applicator), and (3) tree-injection. These application methods are not additive. One to three 

applications may be made for each application method; the maximum single application rate is 

7.1 lb ai/A and the maximum yearly rate is also 7.1 lb ai/A. A pre-harvest interval (PHI) of 0-

days is proposed. Potentially up to 7,500 acres may be treated 

Toxicity/Hazard

Propiconazole has low to moderate toxicity in experimental animals by the oral, dermal and 

inhalation routes, is moderately irritating to the eyes, and minimally irritating to the skin, and it 

is a dermal sensitizer. The primary target organ for propiconazole toxicity in animals is the liver. 

HED’s Hazard Identification Assessment Review Committee (HIARC) concluded that the 

toxicology database for propiconazole is complete for FQPA assessment. Endpoints and dose 

responses have been selected for acute dietary; chronic dietary; short- and intermediate-term 

incidental oral; short-, intermediate-, and long-term dermal; and short-, intermediate-, and longterm inhalation exposures. For the scenarios associated with the new uses, HED concludes that 

the endpoints selected by HIARC are still appropriate. 

The HIARC also concluded that the database was adequate to characterize any potential for 
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prenatal or postnatal risk for infants and children. There is low concern for pre- and/or postnatal 

toxicity resulting from exposure to propiconazole, and no residual uncertainties were identified. 

The exposure databases (dietary food, drinking water, and residential) are complete and the risk 

assessment for each potential exposure scenario includes all metabolites and/or degradates of 

concern and does not underestimate the potential risk for infants and children. The FQPA factor 

is thus 1X. 

The HED Carcinogenicity Peer Review Committee (CPRC) classified propiconazole as Group C 

- possible human carcinogen and recommended that for the purpose of risk characterization the 

Reference Dose (RfD) approach should be used and would be protective. 

Dietary Exposure/Risk Assessment

The nature of propiconazole residues in plants is adequately understood based on the available 

peanut, wheat, grape, rice, celery, and carrot metabolism studies. HED has concluded that for 

plants, residues of propiconazole and all its metabolites convertible to the 2,4-dichlorobenzoic 

acid moiety (2,4-DCBA), including conjugates, are of concern and should be included in the 

dietary (food) risk assessments, and that propiconazole per se should be included in the tolerance 

expression. Propiconazole per se should be included in the dietary (water) risk assessments. 

Propiconazole is also among the group of chemicals which generate the common metabolites, 

1,2,4-triazole (T) and its conjugates triazolylalanine (TA), triazolylacetic acid (TAA) and 

triazolylpyruvic acid (TP). Issues concerning propiconazole and the common triazole 

metabolites are addressed below under a separate heading. 

No acceptable avocado magnitude of the residue data were submitted to support the proposed 

uses. HED has translated and extrapolated available peach field trial data reflecting multiple 

foliar applications with a 3.6 lb/gal EC formulation of propiconazole at 0.11 lb ai/A/application 

and a 0-day PHI. The maximum residue in/on peaches harvested at 0-days PHI, having received 

5 applications of propiconazole at 0.11 lb ai/A/application was 0.78 ppm. Extrapolating for the 

proposed maximum use rate (7.1 lb ai/A/application) to avocado trees, the estimated maximum 

residue level for residues of propiconazole and its metabolites convertible to 2,4-DCBA in/on 

avocado would be 10 ppm. This estimate is expected to be highly conservative given the 

translation of residue data reflecting foliar applications to estimate residues resulting from the 

proposed soil drench, tree-directed (hand-held spray gun/applicator) and tree-injection 

applications to avocado trees. No reasonably reliable data are available for estimating the 

maximum residue level of propiconazole per se in/on avocado for the proposed uses. No triazole 

metabolite data were submitted to support the proposed uses. No Codex, Mexican, or Canadian 

maximum residue limits (MRLs) have been established for residues of propiconazole in/on 

avocado. 

Acute and chronic aggregate dietary (food and drinking water) exposure and risk assessments 

were conducted for propiconazole residues of concern using the Dietary Exposure Evaluation 

Model DEEM-FCIDTM, Version 2.03 which uses food consumption data from the U.S. 

Department of Agriculture’s Continuing Surveys of Food Intakes by Individuals (CSFII) from 

1994-1996 and 1998. 
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The drinking water residues used in the dietary risk assessment were provided by the 

Environmental Fate and Effects Division (EFED) and incorporated directly into this dietary 

assessment. Water residues were incorporated in the DEEM-FCID into the food categories 

“water, direct, all sources” and “water, indirect, all sources.” 

Acute Dietary (Food and Drinking Water) Exposure Results and Characterization

An acute dietary analysis for propiconazole residues of concern was conducted using tolerance 

levels and 100 %CT for all existing and proposed uses. The acute population adjusted dose 

(aPAD) is 0.3 mg/kg/day for all population subgroups (includes females 13-49 years). The 

results of the analysis indicate that acute risk from the dietary exposure (food and water) to 

propiconazole from the requested uses did not exceed HED’s level of concern for the U.S. 

population or any population subgroup. At the 95th percentile, the exposure to the U.S. 

population is at 7 % aPAD; the highest exposed subgroup (Children 1-2 yrs old) is at 17% aPAD. 

Chronic Dietary (Food and Drinking Water) Exposure Results and Characterization

A chronic dietary analysis for propiconazole residues of concern was conducted using tolerance 

levels and 100 %CT for all existing and proposed uses. The chronic population adjusted dose 

(cPAD) is 0.1 mg/kg/day. Results of the analysis indicate that chronic risk from the dietary 

exposure (food and water) to propiconazole from the requested use did not exceed HED’s level 

of concern for the U.S. population or any population subgroup. The exposure to the U.S. 

population is at 7 % cPAD, and the most highly exposed subgroup, Children 1-2 years old, is at 

18 % cPAD. 

Cancer Dietary (Food and Drinking Water) Exposure Results and Characterization

The HED Carcinogenicity Peer Review Committee (CPRC) classified propiconazole as Group C 

- possible human carcinogen and recommended that for the purpose of risk characterization the 

Reference Dose (RfD) approach should be used and would be protective. 

Residential Exposure/Risk Assessment

No new residential uses are being requested at this time. However, adults, adolescents and 

toddlers may be exposed to propiconazole from its currently registered use on turf and 

ornamentals. These risks have been previously assessed. Homeowners can be exposed to 

propiconazole through dermal and inhalation routes while applying home use products. All risk 

calculations were conducted using the maximum turf application rate (1.8 lb ai/acre). None of 

the residential handler exposure scenarios exceeded HED’s level of concern. The residential use 

patterns result in postapplication dermal exposures to adults, and dermal and oral exposures to 

infants and children. These exposures are considered short-term only. In addition to using 

HED’s SOP for residential assessment, chemical specific data on turf transferable residue (TTR) 

was used in the calculation. The dermal and incidental oral exposure to infants and children 

were combined, and all margins of exposures (MOEs) do not exceed the level of concern. Risk 

to children playing on propiconazole-treated structures (from antimicrobial use) was also 

assessed using a screening level assessment; these exposures are considered short- and 

intermediate-term. This risk assessment, based on high end screening-level assumptions, 

indicates no risk of concern. 
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Aggregate Risk Assessment

Aggregate risk assessments were conducted for acute, chronic, short- and intermediate-term 

exposure duration. The risks do not exceed HED’s level of concern. Acute aggregate risk 

included food and water only; chronic aggregate risk also included food and water because no 

chronic exposure from residential uses is expected. Short-term aggregate risk included food, 

water, and residential/antimicrobial exposures. Intermediate-term aggregate risk included food, 

water, and residential exposure to Children 1-2 years old from treated wood used in deck and 

play structures. 

Propiconazole and the Common Triazole Metabolites

Propiconazole is a member of the triazole-derivative fungicide class of pesticides. There is 

currently no evidence to indicate that triazole-derivative fungicides share common mechanisms 

of toxicity and EPA is not following a cumulative risk approach based on a common mechanism 

of toxicity for these pesticides. However, propiconazole, like other triazole-derivative 

fungicides, can form the common metabolites 1,2,4-triazole and its triazole conjugates 

(triazolylalanine, triazolylacetic acid, and triazolylpyruvic acid). To support existing tolerances 

and to establish new tolerances for triazole-derivative pesticides, including propiconazole, U.S. 

EPA conducted a human health risk assessment for exposure to 1,2,4-triazole, triazolylalanine, 

triazolylacetic acid and triazolylpyruvic acid resulting from the use of all current and pending 

uses of any triazole-derivative fungicide. The risk assessment is a highly conservative, 

screening-level evaluation in terms of hazards associated with common metabolites (e.g., use of 

a maximum combination of uncertainty factors) and potential dietary and non-dietary exposures 

(i.e., high end estimates of both dietary and non-dietary exposures). In addition, the Agency 

retained the additional 10X FQPA safety factor for the protection of infants and children. The 

assessment includes evaluations of risks for various subgroups, including those comprised of 

infants and children. The Agency’s complete risk assessment is found in the propiconazole 

reregistration docket at http://www.regulations.gov, Docket Identification (ID) Number EPAHQ-OPP-2005-0497. 

In support of the requested Section 18 Emergency Exemption (ID#10FL02), HED has completed 

an updated dietary exposure and risk analysis for the common triazole metabolites 1,2,4-triazole 

(T), triazolylalanine (TA), triazolylacetic acid (TAA), and triazolylpyruvic acid (TP). [For 

details see the Section 18 Common Triazole Metabolites Updated Dietary Exposure and Risk 

Assessment; HED memo by T. Morton (D380341, 7/27/10).] Acute and chronic aggregate dietary 

(food and drinking water) exposure and risk assessments were conducted using the Dietary 

Exposure Evaluation Model DEEM-FCIDTM, Version 2.03 which uses food consumption data 

from the U.S. Department of Agriculture’s Continuing Surveys of Food Intakes by Individuals 

(CSFII) from 1994-1996 and 1998. No triazole metabolite magnitude of the residue data were 

submitted or are available to support the proposed uses, so the dietary analysis was based on the 

recommended 10 ppm tolerance for residues of propiconazole in/on avocado. 

Four assessments were conducted: acute and chronic durations for T, and acute and chronic 

durations for combined residues of TA, TAA, and TP. All four assessments assume tolerance 

level residues, 100% crop treated and include conservative estimates for residues of the 

metabolites in drinking water. The resulting exposure and risk estimates are based on healthprotective assumptions and should be characterized as conservative. For all four analyses, 
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dietary risk estimates are below HED’s level of concern for all population subgroups. 

Furthermore, the additional dietary exposure/risk from the proposed Section 18 Emergency 

Exemption (ID#10FL02) is deemed so insignificant that a separate common triazole metabolite 

human health aggregate risk assessment in support of the Section 18 registration is not 

warranted. 

With regards to occupational exposure/risk assessment, HED expects that occupational exposure 

to 1,2,4-triazole (residential/occupational exposure to residues of TA, TAA and TP are not 

expected) is likely to occur as a result of activities associated with a single triazole-derivative 

fungicide. The risks associated with occupational exposure to this compound are addressed in 

the risk assessments for the parent compound. Those risk estimates inherently include risk 

associated with occupational exposure to 1,2,4-triazole. Therefore, an occupational exposure 

and risk assessment for 1,2,4-triazole, per se, is not warranted. This is unlike the case for dietary 

exposure where it is likely that multiple triazole-derivative fungicides simultaneously lead to 

1,2,4-triazole exposure. 

Occupational Handler and Postapplication Exposure/Risk Assessment

Occupational handler exposure is expected for certified applicators applying propiconazole to 

avocado trees. Handler risks were assessed using Pesticide Handlers Exposure Database 

(PHED) Version 1.1 (Surrogate Exposure Guide) in the absence of chemical specific data. The 

relevant exposure scenarios for certified applicators applying propiconazole to avocado trees are 

(1) application via handgun sprayer, (2) application via tree injection, and (3) application via soil 

drenching equipment (groundboom). Based on the proposed use patterns, HED expects that 

occupational exposures will generally occur in short-term (1-30 days) durations only. The 

proposed Section 18 label specifies that applicators and other handlers must wear the following 

personal protective equipment (PPE): (1) long-sleeved shirt and long pants, (2) chemicalresistant gloves such as barrier laminate or viton, (3) shoes plus socks, and (4) protective 

eyewear. For all of the occupational handlers exposure scenarios, the non-cancer short-term (1-

30 days) risks are below HED’s level of concern (i.e., MOEs are > 100) with label specific PPE 

and therefore not of concern. 

Based on the use patterns associated with the proposed Section 18 label, HED believes that 

postapplication exposure will be negligible. Therefore, a postapplication quantitative assessment 

was not conducted. 

Environmental Justice Considerations

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). 

Review of Human Research

This risk assessment relies in part on data from the Pesticide Handlers Exposure Database 

(PHED) and the Outdoor Residential Exposure Task Force (ORETF) studies in which adult 

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

been determined to require a review of their ethical conduct, and have received that review. 
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Tolerance Recommendations

HED has no concerns regarding human health exposure and risk from the proposed Section 18 

use of propiconazole on avocado trees in commercial orchards of Florida to control laurel wilt. 

A time-limited tolerance should be established for residues of propiconazole per se at 10 ppm 

in/on avocado. 

Notes to RD: 

(1) The Section 18 submission indicates that IR-4 in conjunction with Syngenta Crop 

Protection and the University of Florida/IFAS are planning magnitude of the 

residue trials in 2010 to support a Section 3 registration for the use of propiconazole 

on avocado trees. Given the unique application methods for this use when 

compared to other propiconazole agricultural uses, a study protocol might be 

advisable. In any case, these parties should be reminded that because propiconazole 

is a triazole-derivative fungicide, HED requires that samples from any metabolism, 

feeding, field trial, and/or processing studies be analyzed for the triazole metabolites 

triazolylalanine (TA), triazolylacetic acid (TAA), triazolylpyruvic acid (TP) and 

1,2,4-triazole (T). Guidance has been issued concerning these residue chemistry 

data requirements for the triazole-based metabolites under DP# 327788 (4/25/06, M. 

Doherty). 

(2) Although the Propiconazole RED (July, 2006) has previously recommended that the 

tolerance expression should be parent only, the current tolerance expression 

specified in 40 CFR §180.434 is for residues of propiconazole and its metabolites 

determined as 2,4-dichlorobenzoic acid (2,4-DCBA) and expressed as parent 

compound. In anticipation of the implementation of this recommendation, it might 

be advisable to analyze samples for residues of propiconazole per se as well as for 

residues of propiconazole and its metabolites determined as 2,4-dichlorobenzoic acid 

(2,4-DCBA) and expressed as parent compound. 

2.0 INGREDIENT PROFILE

Propiconazole is a triazole-derivative fungicide that provides broad spectrum disease control 

through inhibition of sterol biosynthesis in fungi. 

2.1 Proposed New Uses

The Florida Department of Agriculture and Consumer Services has requested an emergency 

specific exemption to use propiconazole to control laurel wilt on avocado trees in commercial 

orchards of Florida; potentially treating up to 7,500 acres. The product to be used is Tilt®

Fungicide (EPA Reg. No. 100-617), a 3.6 lb/gal emulsifiable concentrate (EC) formulation 

containing 41.8% propiconazole by weight. 
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Application methods include: (1) soil drench (groundboom), (2) tree-directed (hand-held spray 

gun/applicator), and (3) tree-injection. These application methods are not additive. One to three 

applications may be made for each application method; the maximum single application rate is 

7.1 lb ai/A and the maximum yearly rate is also 7.1 lb ai/A. A pre-harvest interval (PHI) of 0-

days is proposed. The proposed use directions are summarized in Table 2.1. 

Table 2.1. Summary of Proposed Directions for Use of Propiconazole on Avocado Trees. 

Applic. Timing, 

Type, and Equip. 

Formulation 

[EPA Reg. 

No.] 

Applic. 

Rate 

(lb ai/A) 

Max. No. 

Applic. per 

Season 

Max. Seasonal 

Applic. Rate 

(lb ai/A/year) 

PHI 

(days) 

Use Directions and 

Limitations 

Soil drench 

3.6 lb/gal EC 

[100-617] 

7.1 1-3 7.1 0 

These methods of 

application are not 

additive. 

Trees should be treated 

when sap is actively moving 

up in the trees, not during 

dormant periods. 

It is expected that a single 

application per year will be 

sufficient. 

The use of an adjuvant is 

recommended for treedirected applications. 

This pesticide is toxic to 

fish. Do not apply directly 

to water, or to areas where 

surface water is present, or 

to intertidal areas below the 

mean high water mark. 

Tree-directed 

(hand-held spray 

gun/applicator) 

7.1 1-3 7.1 0 

Tree-injection 7.1 1 7.1 0 

The proposed Section 18 label specifies that applicators and other handlers must wear the 

following personal protective equipment (PPE): (1) long-sleeved shirt and long pants, (2) 

chemical-resistant gloves such as barrier laminate or viton, (3) shoes plus socks, and (4) 

protective eyewear. A restricted entry interval (REI) of 12 hours is specified. 

 
Page 11 of 31 

2.2 Structure and Nomenclature

Table 2.2. Test Compound Nomenclature 

Chemical Structure 

Cl

Cl

O

O

N

N

N

CH3

Empirical Formula C15H17Cl2N3O2

Common name Propiconazole 

Company experimental name CGA-64250 

IUPAC name 1-((2-(2,4-Dichlorophenyl)-4-propyl-1,3-dioxolan-2-yl)methyl)-1H-1,2,4-triazole 

CAS name 1H-1,2,4-Triazole, 1-((2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-2-yl)methyl)- 

CAS Registry Number 60207-90-1 

End-use product/EP Tilt® Fungicide 41.8% ai or 3.6 lb/gal (EPA Reg. No. 100-617) 

Chemical Class Triazole 

Known Impurities of Concern None 
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2.3 Physical and Chemical Properties 

All pertinent product chemistry data requirements have been satisfied for the Novartis 95% 

T/TGAI, except that additional data are required concerning stability and UV/visible absorption 

(OPPTS 830.6313 and 7050). 

Table 2.3. Physicochemical Properties 

Parameter Value Reference 

Molecular Weight 342.23 MRID No.: 40583701 

Boiling point/range >250°C at 101.325 kPa, 120°C 

at 1.9 Pa 

MRID No.: 43698701 

pH 4.9 @ 25°C (1% aqueous 

dispersion) 

MRID No.: 43698701 

Density 1.289 g/cm3 typical @ 20°C MRID No.: 43698701 

Water solubility (20 °C) 0.10 g/L at 20°C MRID No.: 41720301 

Solvent solubility (temperature not specified) Completely miscible in ethanol, 

acetone, toluene and n-octanol. 

n-hexane = 47 g/L 

MRID No.: 42030201 

Vapor pressure (25°C) 4.2 x 10-7 mmHg @ 25°C MRID No.: 41720301 

Dissociation constant, pKa pKa 1.09 MRID No.: 43698701 

Octanol/water partition coefficient, Log 

(KOW) (25 °C) 

3.72 @ pH 6.6 MRID No.: 43698701 

UV/visible absorption spectrum (λmax, nm) Not available 

3.0 HAZARD ASSESSMENT

For a detailed discussion, refer to: Propiconazole FQPA Human Health Risk Assessment for the Section 3 

Registrations on Garden Beets, Turnips, Parsley, Cilantro and Pineapple; HED memo by Y. Donovan (D347905, 

9/30/08).

3.1 Hazard Profile 

Propiconazole has low to moderate toxicity in experimental animals by the oral (Category III), 

dermal (Category III) and inhalation routes (Category IV). It is moderately irritating to the eyes 

(Category III), and minimally irritating to the skin (Category IV). It is a dermal sensitizer. 

Propiconazole is readily absorbed by the rat skin with absorption within 10 hours of dermal 

application. The acute toxicity profile of propiconazole is summarized in Table 3.1. 
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Table 3.1. Acute Toxicity Profile of Propiconazole 

G. L. 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 hrs III 

870.2500 Primary Skin Irritation 00058598 No irritation IV 

870.2600 Dermal Sensitization 44949501 Not a sensitizer - 

The primary target organ for propiconazole toxicity in animals is the liver. Increased liver 

weights were seen in mice after subchronic or chronic oral exposures to propiconazole at doses 

>50 mg/kg/day. Liver lesions such as vacuolation of hepatocytes, ballooned liver cells, foci of 

enlarged hepatocytes, hypertrophy and necrosis are characteristic of propiconazole toxicity in 

rats and mice. Mice appear to be more susceptible to its toxicity than rats. Decreased body 

weight gain in experimental animals was seen in subchronic, chronic, developmental and 

reproductive studies. Dogs appeared to be more sensitive to the localized toxicity of 

propiconazole as manifested by stomach irritation at 6 mg/kg/day and above. 

In rabbits, developmental toxicity occurred at a higher dose than the maternal toxic dose, while 

in rats, developmental toxicity occurred at lower doses than maternal toxic doses. Increased 

incidences of rudimentary ribs occurred in rat and rabbit fetuses. Increased cleft palate 

malformations were noted in two studies in rats. In one published study in rats developmental 

effects (incomplete ossification of the skull, caudal vertebrae and digits, extra rib (14th rib) and 

missing sternebrae, malformations of the lung and kidneys) were reported at doses that were not 

maternally toxic. 

In the two generation reproduction study in rats, offspring toxicity occurred at a higher dose than 

the parental toxic dose suggesting lower susceptibility of the offspring to the toxic doses of 

propiconazole in this study. 

Propiconazole was negative for mutagenicity in the in vitro BALB/ C 3T3 cell transformation 

assay, bacterial reverse mutation assay, Chinese hamster bone marrow chromosomal aberration 

assay, unscheduled DNA synthesis studies in human fibroblasts and primary rat hepatocytes, 

mitotic gene conversion assay and the dominant lethal assay in mice. Hepatocellular 

proliferation studies in mice suggest that propiconazole induces cell proliferation followed by 

treatment-related hypertrophy in a manner similar to the known hypertrophic agent 

phenobarbital. 

Propiconazole was carcinogenic to CD-1 male mice. Propiconazole was not carcinogenic to rats 

or to female mice. The HED Carcinogenicity Peer Review Committee (CPRC) classified 

propiconazole as Group C - possible human carcinogen and recommended that for the purpose of 

risk characterization the Reference Dose (RfD) approach be used for quantification of human 

risk (HED Doc. No. TX0009771, April 15, 1992 meeting). 
Page 14 of 31 

3.2 FQPA Hazard Considerations

HIARC (HED Doc. No. TX0052277, February 13, 2003 meeting) concluded that the toxicology 

database for propiconazole is complete for FQPA assessment. The HIARC concluded that there 

is low concern for pre- and/or postnatal toxicity resulting from exposure to propiconazole. In the 

developmental toxicity study in rats, the HIARC considered the fetal effects observed in this 

study at a dose lower than that evoking maternal toxicity to be quantitative evidence of increased 

susceptibility of fetuses to in utero exposure to propiconazole. In the developmental toxicity 

study in rabbits, the HIARC determined that neither quantitative nor qualitative evidence of 

increased susceptibility of fetuses to in utero exposure to propiconazole was observed in this 

study. In the 2-generation reproduction study in rats, the HIARC determined that neither 

quantitative nor qualitative evidence of increased susceptibility of neonates (as compared to 

adults) to pre- and/or postnatal exposure to propiconazole was observed in this study. Since 

there was quantitative evidence of increased susceptibility of the young following exposure to 

propiconazole in the developmental rat study, HIARC performed a Degree of Concern Analysis 

and concluded that the degree of concern for the effects observed in this study was low and no 

residual uncertainties were identified. The FQPA factor is thus 1X. 

3.3 Summary of Toxicity Endpoint Selection

Table 3.3. Propiconazole: Summary of Toxicological Dosages and Endpoints Selected for Human Health Risk 

Assessments.

Exposure 

Scenario

Doses Used in Risk 

Assessment, UF 

FQPA SF and Level 

of Concern for Risk 

Assessment

Study and Toxicological Effects

Acute Dietary 

(Females 13-49) 

NOAEL = 30 mg 

ai/kg/day 

UF =100 

Acute RfD = 0.3 

mg/kg/day 

FQPA SF = 1X 

aPAD = 

acute RfD

 FQPA SF 

= 0.3 mg/kg/day 

Developmental Toxicity Study - Rats. 

Developmental toxicity: increased incidence of 

rudimentary ribs, cleft palate malformations (0.3%), 

unossified sternebrae, as well as increased incidence 

of shortened and absent renal papillae. 

Acute Dietary 

(General Population 

including infants and 

children) 

NOAEL = 30 mg 

kg/day 

UF =100 

Acute RfD =0.3 

mg/kg/day 

FQPA SF = 1X 

aPAD = 

acute RfD

 FQPA SF 

=0.3 mg/kg/day 

Acute Neurotoxicity Study – Rats. 

Clinical signs (piloerection, diarrhea, tiptoe gait). 

Chronic Dietary 

(All populations) 

NOAEL = 10 mg 

ai/kg/day 

UF = 100 

Chronic RfD = 0.1 

mg/kg/day 

1X 

cPAD = 

chronic RfD

 FQPA SF 

=0.1 mg/kg/day 

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) Incidental 

Oral 

NOAEL = 30 mg 

kg/day 

Residential MOE = 

100 

Occupational = NA 

Acute Neurotoxicity Study – Rats. 

Clinical signs (piloerection, diarrhea, tiptoe gait). 
Page 15 of 31 

Table 3.3. Propiconazole: Summary of Toxicological Dosages and Endpoints Selected for Human Health Risk 

Assessments.

Exposure 

Scenario

Doses Used in Risk 

Assessment, UF 

FQPA SF and Level 

of Concern for Risk 

Assessment

Study and Toxicological Effects

 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 

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 

dermal (1 - 6 months) 

and Long-Term 

dermal 

(>6 months) 

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) 

Short-Term 

(1 - 30 days) 

Inhalation 

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) and LongTerm Inhalation 

(>6 months) 

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, and RfD approach for risk characterization. 

UF = uncertainty factor, FQPA SF = FQPA safety factor, NOAEL = no observed adverse effect level, LOAEL = 

lowest observed adverse effect level, PAD = population adjusted dose (a = acute, c = chronic) RfD = reference dose, 

MOE = margin of exposure. 

As per the FQPA of 1996, when there is potential for residential exposure to the pesticide, 

aggregate risk assessment must consider exposures from all routes, such as oral, dermal and 

inhalation. The toxicity endpoints selected for these routes of exposure may be aggregated as 

follows: the oral, dermal, and inhalation routes of exposure can be combined to assess aggregate 

risks because of the selection of a common toxicity endpoint for all routes and durations of 

exposure. 
Page 16 of 31 

3.4 Endocrine Disruption

The Agency is required under the Federal Food, Drug and Cosmetic Act (FFDCA), as amended 

by FQPA, to develop a screening program to determine whether certain substances (including all 

pesticide active and other ingredients) “may have an effect in humans that is similar to an effect 

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

may designate.” In the available toxicity studies on propiconazole, there was no observed 

estrogen, androgen, and/or thyroid mediated toxicity. When additional appropriate screening 

and/or testing protocols become available, propiconazole may be subjected to further screening 

and/or testing to better characterize the effects related to endocrine disruption. 

4.0 DIETARY EXPOSURE/RISK CHARACTERIZATION

Propiconazole is among the group of chemicals which generate the common triazole metabolites, 

1,2,4-triazole and its conjugates triazolylalanine, triazolylacetic acid and triazolylpyruvic acid. 

Issues concerning propiconazole and the common triazole metabolites have been addressed 

under a separate heading in the Executive Summary only. 

4.1 Residue Chemistry Profile

Since the proposed Section 18 is for the use of propiconazole on avocado trees in commercial 

orchards of Florida, the following residue chemistry guideline topics are not relevant and will not 

be discussed further: (1) GLN 860.1300 Nature of the Residue in Livestock; (2) GLN 860.1480 

Meat, Milk, Poultry, and Eggs; (3) GLN 860.1520 Processed Food and Feed; and (4) GLN 

860.1850 and 860.1900 Confined and Field Accumulation in Rotational Crops. 

The nature of propiconazole residues in plants is adequately understood based on the available 

peanut, wheat, grape, rice, celery, and carrot metabolism studies. HED has concluded that for 

plants, residues of propiconazole and all its metabolites convertible to the 2,4-dichlorobenzoic 

acid moiety (2,4-DCBA), including conjugates, expressed as parent, are of concern and should 

be included in the dietary (food) risk assessments, and that propiconazole per se should be 

included in the tolerance expression. Propiconazole per se should be included in the dietary 

(water) risk assessments. 

For enforcing the proposed tolerance, a gas chromatography (GC) method using flame ionization 

detection (Method AG-354) is available for determining residues of propiconazole per se in/on 

plant commodities, with a limit of quantitation (LOQ) of 0.05 ppm. In addition, FDA’s PAM 1 

Multiresidue Methods Section 302 may be used to determine parent propiconazole in both plant 

and livestock matrices. 

No acceptable avocado magnitude of the residue data were submitted to support the proposed 

uses. Stone fruit field trial data reflecting multiple foliar applications were previously submitted 

and reviewed by the Agency (MRID 41063802; PP#9F3758; No DP Barcode #, S. Malak, 

11/28/89). In these tests, a 3.6 lb/gal EC formulation of propiconazole was applied 3-5 times by 

air or ground using 50 or 100 g ai/A/application (0.11 or 0.22 lb ai/A/application). Fresh 
Page 17 of 31 

samples of apricots, nectarines, peaches, and plums were taken at various harvest intervals of 0, 

3, and 7 days after the last application. Samples were analyzed with an analytical method, AG454, that determined residues of propiconazole and its metabolites convertible to the 2,4-

dichlorobenzoic acid (2,4-DCBA) moiety using a gas chromatography method with electron 

capture detection (GC/ECD). Results were reported as propiconazole equivalents. [Note: 

Method AG-454 if an earlier version of Method AG-454A which is published in PAM II as an 

acceptable enforcement method.] The maximum residue level found was 0.78 ppm in/on a 

whole peach sample collected 0-days after the last of 5 foliar applications at 50 g 

ai/A/application (0.11 lb ai/A/application); total application was 0.55 lb ai/A. [Note: The 

reviewer notes that given the retreatment intervals, only the last two applications are likely to 

have had a significant effect on the resulting residue level.] Extrapolating these data to reflect an 

application rate of 7.1 lb ai/A, the maximum residues of propiconazole in/on peaches would be 

estimated at 10 ppm. Based on these data, the estimated maximum residue level for residues of 

propiconazole and its metabolites convertible to 2,4-DCBA in/on avocado would be 10 ppm. 

This estimate is expected to be highly conservative given the translation of residue data 

reflecting foliar applications to estimate residues resulting from the proposed soil drench, treedirected (hand-held spray gun/applicator) and tree-injection applications to avocado trees. No 

reasonably reliable data are available for estimating the maximum level of propiconazole per se 

in/on avocado for the proposed uses; hence, the time-limited tolerance level will also have to be 

established at 10 ppm. No triazole metabolite data were submitted or are available to support the 

proposed uses. 

[Note: The subject Section 18 submission did provide a report of the results of an Australian 

magnitude of the residue study on avocado reflecting foliar applications of propiconazole (1993; 

Bull and Bodnaruk) and several worksheets with no details concerning the results of a US 

magnitude of the residue study reflecting soil drench and tree-injection applications of 

propiconazole to avocado trees (2010; Task No. TK0015676; R. Ploetz, University of Florida). 

Neither study was deemed adequate for the purposes of estimating residues for the dietary risk 

assessment or for establishing a tolerance for the proposed uses. However, it should be noted 

that the US data (2009; Task No. TK0015676; R. Ploetz, University of Florida) do suggest that a 

tree-injection application of propiconazole will result in detectable, and possibly significant, 

residue levels of propiconazole in/on avocado. These data are considered supplemental in nature 

and scope and suggest that the recommended time-limited tolerance (10 ppm), based on the 

peach field trial data, is highly conservative.] 

The Codex Alimentary Commission has established several maximum residue limits (MRLs) for 

propiconazole in/on various raw agricultural commodities. In addition, both Canada and Mexico 

have established MRLs for propiconazole in/on various commodities. The Codex and Mexican 

MRLs are expressed in terms of propiconazole per se. The Canadian MRLs are expressed in 

terms of combined residues of propiconazole and its metabolites containing the 2,4-DCBA 

moiety. No Codex, Mexican, or Canadian MRLs have been established for residues of 

propiconazole in/on avocado. 
Page 18 of 31 

4.2 Drinking Water Profile

The drinking water residues used in the dietary risk assessment were provided by the 

Environmental Fate and Effects Division (EFED) in the following memorandum: “Drinking 

Water Assessment for Propiconazole Uses on Florida Avocado – Section 18 Emergency 

Exemption” (Jim Lin, 07/15/10, D379850). 

The proposed new uses to avocado trees do not result in higher EDWCs than those estimated for 

the existing turf use which are based on 8 applications at a rate of 0.786 lb ai/A with a 14-day 

interval. Therefore, the drinking water assessment was based on the existing turf use rate. 

The PRZM/EXAMS estimated surface water drinking water concentrations for propiconazole 

are: 

55.78 ug /L for the 1 in 10 year annual peak concentration (acute) 

21.61 ug /L for the 1 in 10 year annual mean concentration (non-cancer chronic) and 

13.24 ug /L for the 30 year annual mean concentration (cancer chronic). 

The SCI-GROW estimated ground water drinking water concentrations for propiconazole are 

not expected to exceed 0.64 μg/L

The model and its description are available at the EPA internet site: 

http://www.epa.gov/oppefed1/models/water/. 

4.3 Dietary Exposure and Risk Assessment

For a detailed discussion refer to: Acute and Chronic Aggregate Dietary (Food and Drinking Water) Exposure and 

Risk Assessments for the Section 18 Registration on Avocado in Florida; HED memo by T. Morton, D380158, 

7/21/10. 

Propiconazole acute and chronic aggregate dietary (food and drinking water) exposure and risk 

assessments were conducted using the Dietary Exposure Evaluation Model software with the 

Food Commodity Intake Database DEEM-FCIDTM, Version 2.03 which uses food consumption 

data from the U.S. Department of Agriculture (USDA’s) Continuing Surveys of Food Intakes by 

Individuals (CSFII), 1994-1996 and 1998. The analyses were performed to support the Section 

18 registration on avocado. 

 

Acute Dietary (Food and Drinking Water) Exposure Results and Characterization

An acute dietary analysis for propiconazole residues of concern was conducted using tolerance 

levels, including the recommended 10 ppm tolerance in/on avocado, and 100 %CT for all 

existing and proposed uses. The highest estimates from surface water (acute, 55.8 ppb) were 

directly entered into the exposure model to assess the contributions from drinking water. The 

acute PAD is 0.3 mg/kg/day for all population subgroups (includes females 13-49 years). The 

results of the analysis indicate that acute risk from the dietary exposure (food and water) to 

propiconazole from the requested uses did not exceed HED’s level of concern for the U.S. 

population or any population subgroup. At the 95th percentile, the exposure to the U.S. 

population is at 7 % aPAD; the highest exposed subgroup (Children 1-2 yrs old) is at 17% aPAD. 
Page 19 of 31 

Chronic Dietary (Food and Drinking Water) Exposure Results and Characterization

A chronic dietary analysis for propiconazole residues of concern was conducted using tolerance 

levels, including the recommended 10 ppm tolerance in/on avocado, and 100 %CT for all 

existing and proposed uses. The highest estimates from surface water (chronic, 21.6 ppb) were 

directly entered into the exposure model to assess the contributions from drinking water. The 

cPAD is 0.1 mg/kg/day. Results of the analysis indicate that chronic risk from the dietary 

exposure (food and water) to propiconazole from the requested use did not exceed HED’s level 

of concern for the U.S. population or any population subgroup. The exposure to the U.S. 

population is at 7 % cPAD, and the most highly exposed subgroup, Children 1-2 years old, is at 

18 % cPAD. 

Cancer Dietary (Food and Drinking Water) Exposure Results and Characterization

The HED Carcinogenicity Peer Review Committee (CPRC) classified propiconazole as Group C 

- possible human carcinogen and recommended that for the purpose of risk characterization the 

Reference Dose (RfD) approach should be used and would be protective. 

Results and Discussion

At the 95th percentile, the acute dietary exposure (food and water) to general US population is at 

7 % of the aPAD, and the most highly exposed subgroup, Children 1-2 yrs old, is at 17 % of the 

aPAD. The chronic dietary exposure to general US population is at 7 % of the cPAD, and the 

most highly exposed subgroup, Children 1-2 yrs old, is at 18 % of the cPAD. All the dietary risk 

estimates are below 100% of the PADs. 

These analyses are highly conservative, Tier 1 dietary exposure assessments. Further refinement 

to the analyses could be made through the use of anticipated residues, incorporation of 

percentages of crops treated with propiconazole, and/or monitoring data that better reflect 

residues at the time of consumption. Since risk estimates are well below HED’s level of 

concern, a more highly refined analysis is not needed at this time. 

These Tier 1 analyses demonstrate that the requested uses for propiconazole will not result in 

dietary risk estimates that exceed HED’s level of concern for any of the regulated population 

subgroups, including those comprised of infants and children. A summary of the dietary 

exposure and risk analyses is given in Table 4.3. 
Page 20 of 31 

Table 4.3. Summary of Dietary Exposure and Risk for Propiconazole (Food + Water). 

Population Subgroup* 

Acute Dietary 

(95th Percentile) Chronic Dietary Cancer 

Dietary 

Exposure 

(mg/kg/day) % aPAD 

Dietary 

Exposure 

(mg/kg/day) % cPAD 

Dietary 

Exposure 

(mg/kg/day) Risk 

General U.S. Population 0.022029 7 0.006790 7 

N/A 

All Infants (< 1 year old) 0.048212 16 0.015833 16 

Children 1-2 years old 0.051513 17 0.018203 18 

Children 3-5 years old 0.039626 13 0.014752 15 

Children 6-12 years old 0.027152 9 0.009621 10 

Youth 13-19 years old 0.018020 6 0.005886 6 

Adults 20-49 years old 0.017909 6 0.005682 6 

Adults 50+ years old 0.013501 5 0.004553 5 

Females 13-49 years old 0.016758 6 0.005366 5 

5.0 RESIDENTIAL (NON-OCCUPATIONAL) EXPOSURE/RISK 

CHARACTERIZATION

5.1 Residential Handler Exposure and Risk Characterization

No new residential uses are being requested at this time. However, adults, adolescents and 

toddlers may be exposed to propiconazole from its currently registered uses on turf, ornamentals, 

and treated paints. 

These risks have been previously assessed. 

Propiconazole: Revised Occupational and Residential Exposure Assessment; James Miller, Environmental 

Scientist (D329393, 6/15/06) 

Propiconazole Occupational and Residential Exposure Assessment of the Antimicrobial Uses; Timothy 

Leighton (D326306, 2/1/2006) 

Amendment to the Propiconazole RED for Children’s Postapplication Exposure from Treated Structures; 

Tim Leighton (D330159, 06/20/06) 
Page 21 of 31 

The anticipated use patterns and current labeling indicate three major residential exposure 

scenarios based on the types of equipment and techniques that can potentially be used to make 

propiconazole applications. The quantitative exposure/risk assessment developed for residential 

handlers is based on these scenarios: 

• Mixer/Loader/applying liquids and wettable powder in water soluble packets via 

1) Low Pressure Handwand, and 2) Hose-End Sprayer. 

• Applying treated paint using airless sprayer and Hose-end spray. 

Residential handler exposure scenarios are considered to be short-term only due to the infrequent 

uses associated with homeowner products. 

A series of assumptions and exposure factors served as the basis for completing the residential 

handler risk assessments. Each assumption and factor is detailed below. In addition to these 

factors, unit exposures were used to calculate risk estimates. Mostly, these unit exposures were 

taken from the Pesticide Handlers Exposure Database (PHED) and the Outdoor Residential 

Exposure Task Force (ORETF) studies. 

HED believes that the scenarios assessed in this document represent worst-case exposures and 

risks resulting from use of propiconazole in residential environments. It should also be noted 

that there were many other scenarios where medium to low quality PHED data were used to 

complete the assessment. Data quality should be considered in the interpretation of the 

uncertainties associated with each risk presented. 

• Short-term estimated risks for residential handlers are presented below in Table 5.1. All 

estimated risks are below HED’s level of concern (i.e., MOEs are > 100) assuming 

handlers are wearing short-sleeve shirt, short pants, shoes, and socks. 
Page 22 of 31 

Table 5.1. Summary of Residential Handler Exposure Estimates 

Application. Equip. Crop(s)/Site 

Max Appl. 

Rate1 

Daily Area 

Treated2 

Handler 

Scenario Short-Term 

MOE 

 Lb ai/Acre 

or 

% in paint* 

Acre/day 

Or gal/day* M/L/A Derml+Inhln Baseline 

Low Pressure 

Handwand Ornamentals (woody 

and flowering plants), 

Shade Trees, Woody 

Shrubs and Vines 

0.0024 

5* (Liquids) 4400 

 (WP/WSP) N/A 

Hose-end 

Sprayer 5* (Liquids) 40,000 

 (WP/WSP) N/A 

Low Pressure 

Handwand 

Turf 

(Lawns) 1.8 

0.023 

 (Liquids) 1300 

 (WP/WSP) N/A 

Hose-end 

Sprayer 0.5 (Liquids) 530 

 (WP/WSP) N/A 

Brush/Roller3 

Applying treated paint 

0.35% 15* (Paint) 330 

Airless Sprayer3 2* (Paint) 120

Notes: 

1 Application rates are the maximum rates provided for propiconazole in all cases. 

2 Amount handled per day values are HED estimates of area treated or gallons applied based on Exposure SAC SOP 

#12 “Recommended Revisions to the Standard Operating Procedures for Residential Exposure Assessments,” HED 

estimates and AD Standard Assumptions. 

3

 Paint exposure scenarios are from the AD Occupational and Residential Exposure Assessment (T. Leighton, 

2/1/2006, D326306). The density of paint is assumed to be 10 lb/gal. 

None of the residential handler exposure scenarios exceeded HED’s level of concern. [Note: 

Although the risk for mixing/loading/applying propiconazole with a low pressure handwand is 

not a concern, (MOE = 1300) it is important to note that most labels identify a hose-end sprayer 

as the method of application. Additionally, all risk calculations were conducted using the 

maximum turf application rate (1.8 lb ai/acre). However, a turf application rate of 0.51 lb ai/acre 

was identified on a residential-use product label (EPA Reg # 100-773). This lower application 

rate may better represent homeowner use. 

5.2 Residential Postapplication Exposure and Risk Characterization

The existing residential use patterns result in postapplication dermal exposures to adults, and 

dermal and oral exposures to infants and children. These exposures are considered short-term 

only, due to the fact that postapplication exposures were calculated using propiconazole as the 

parent compound, while compound specific TTR data indicates that at the Indiana, California, 

and Pennsylvania test sites, average total propiconazole residues declined to below the minimum 

quantifiable limit (MQL) by DAT = 14, DAT = 10, and DAT = 8 respectively. These dissipation 
Page 23 of 31 

rates, combined with label specific use rates and frequency of use specifications, reinforce the 

hand to mouth short-term exposure scenario; For short-term exposure to Children 1-2 years old, 

the driving factors for this risk assessment are hand to mouth, object to mouth, and dermal 

exposure. Soil ingestion is insignificant (MOE>300,000) compared to these factors, indicating 

that the postapplication scenario should be short-term only 

In addition to using HED’s SOP for residential assessment, the study specific turf transferable 

residue (TTR) was used in the calculation. A summary of risk estimates for residential 

postapplication risks for adults and children is provided in the following tables. 

Table 5.2.1. Short-term Risks to Adults and Children From Postapplication Exposure to Turf . 1

Exposure scenarios Max. appl. rate 

(lb ai/A) 

Exposure 

routes 

TC 

 cm2/hr 

Short-term 

MOE 2

 Adult, high-contact activities 1.8 dermal 70,000 350 

 Adult, mowing 1.8 dermal 500 50,000 

 Toddler, high contact activities 1.8 dermal 25,000 210 

 Toddler, hand-to-mouth activity 1.8 oral N/A 1,100 

 Toddler, object-to-mouth activity 1.8 oral N/A 4,500 

 Toddler, incidental soil ingestion 1.8 oral N/A 330,000

1. HED memo by J. Miller (D329393, 6/15/06). 

2. Dermal exposure only. 

The postapplication exposure results summarized in Table 5.2.1 a were not recalculated using the 

current TCs to bring this assessment up to today's standards, even though chemical-specific turf 

transferable residue (TTR) studies are available for such scenarios (J. Miller, D329393, 

6/15/2006). The TTR data were generated using the Modified California Roller Technique 

(ORETF roller) in all the three locations. According to the ExpoSAC Policy No. 12, the TTR 

data generated by the ORETF roller have a lower transfer efficiency (<0.5-1%) than that for the 

revised TCs (1-5%). Therefore, the ExpoSAC Policy No. 12 guidance document advised against 

using the ORETF roller TTR data in conjunction with the revised TCs because it results in lower 

exposures to adults and children than the exposures estimated according by the current 

residential SOP standards. 

The aggregated risk to Toddlers from exposures to residential turf use is illustrated in Table 

5.2.2. As shown in Table 5.2.2, the aggregate MOE is 170 which is not of concern.
Page 24 of 31 

Table 5.2.2. Toddler Residential Risk Estimates for Postapplication Exposure to Propiconazole 

Exposure Scenario 

TC 

cm2/hr 

Route of 

Exposure Application Rate MOE at Day 0 Combined MOE 

Outdoors

Hand to Mouth Activity on 

Turf N/A Oral 1.8 lb ai/acre 1100 

170 Object to Mouth Activity on 

Turf N/A Oral 1.8 lb ai/acre 4500 

Soil Ingestion N/A Oral 1.8 lb ai/acre 330,000 

Turf – General High-Contact 

Activities 25000 Dermal 1.8 lb ai/acre 210 

Note: Combined MOE = NOAEL/(ADDhand-to-mouth + ADDobject-to-mouth + ADDincidental soil ingestion + ADDdermal) 

Level of Concern: MOE = 100 

 

Residential postapplication scenarios from antimicrobial uses were also assessed. No 

postapplication exposure to adult is expected because of propiconazole’s low vapor pressure 

(therefore, no inhalation exposure) and the registrants’ deletion of the only other use (i.e., 

materials preservative in fabrics, textiles, area carpet fibers). Propiconazole is used on many 

different types of wood including 1) green or fresh cut lumber, poles, posts, and timbers; 2) 

manufactured wood products such as logs (including for log home construction), wood 

chips/sawdust, plywood veneer, and particle board; 3) dry lumber; and 4) finished wood products 

such as millwork, shingles, shakes, siding, plywood, and structural lumber and composites. 

Except “dry lumber” uses, the other 3 groupings would result in minimal dermal and/or 

incidental oral exposure. Inhalation exposure (e.g., in log homes treated with propiconazole) is 

also expected to be negligible based on the low vapor pressure. For “dry lumber” uses, if 

propiconazole-treated lumber is used to build residential decks and/or play sets, then there is the 

potential for dermal and incidental oral exposures to treated lumber used in decks and or play 

sets. AD assessed the risk to children playing on propiconazole-treated structures using 

screening level assessment. Table 5.2.3 shows the result of aggregate risk from incidental oral 

and dermal exposure from propiconazole treated wood. This risk assessment, based on high end 

screening-level assumptions, indicates no risk of concern. Confirmatory data for the surface 

residues are needed to verify this screening-level assessment. 

Table 5.2.3. Propiconazole Assessment of Children Playing on Treated Structures. 

Exposure Dose (mg/kg/day)a MOEs (Target =100)b

Short-term Intermediate 

Dermal Contact 0.0675 450 150 

Incidental Oral 0.00563 5,300 1,800 

Aggregate 0.0731 410 140 

a Aggregate dose = dermal dose + oral dose. 

b MOEs = ST and IT NOAELs (mg/kg/day) / Dose (mg/kg/day). Where ST NOAEL = 30 mg/kg/day and IT 

NOAEL = 10 mg/kg/day. Target MOE = 100. 

 
Page 25 of 31 

6.0 AGGREGATE RISK ASSESSMENTS AND RISK CHARCTERIZATION

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 and Chronic Aggregate Risk

Acute and chronic aggregate exposures include food plus drinking water exposures. Acute and 

chronic aggregate risks are not of concern. See Section 4.3 for details. 

6.2 Short-Term Aggregate Risk

Short-intermediate term aggregate exposure takes into account residential exposure plus average 

exposure levels to food and water (considered to be a background exposure level). Based on the 

residential use pattern, propiconazole postapplication exposures to adults are from dermal 

exposure only, for infants and children are from dermal and oral routes. Table 6.2.1 aggregates 

the short-term risk for Toddlers from incidental oral, dermal, and food and water (as a 

background). Although both residential and antimicrobial uses result in incidental oral and 

dermal exposure to children, the highest incidental oral and dermal exposure scenarios are from 

residential use on turf, which were used in the short-term aggregate risk assessment. The shortterm aggregate risk does not exceed HED’s level of concern. This assessment is considered very 

conservative in that the residential incidental oral postapplication exposure was calculated by 

combining three screening level assessments (which by themselves already have conservative 

estimates). HED also did a back-calculation to estimate room available in the risk cup for shortterm aggregate risk. In order to obtain a short-term aggregate MOE ≥ 100, the MOE resulting 

from additional short-term exposures to Children 1-2 (from possible dermal and incidental oral 

exposure from treated wood or other sources) needs to be ≥ 270. As stated above in Section 5.2 

(see Table 5.2.3), the combined short-term MOE (dermal and incidental oral) from antimicrobial 

use of propiconazole in treated wood for Toddler is 410, which is greater than 270. 
Page 26 of 31 

Table 6.2.1. Short-term Aggregate Risk Estimates to Propiconazole for Toddler (Children 1-2years)

Exposure Scenario 

Target 

MOE Route of 

Exposure Exposure NOAELs MOE at Day 0 Combined MOE5

Average Food and Water 

(As background) 

N/A Food and 

water 0.0182 30 1650 2

160 

Hand to Mouth Activity on 

Turf 100 1

 Oral 0.0269 30 1100 3

Object to Mouth Activity on 

Turf 100 1

 Oral 0.0067 30 4500 3

Soil Ingestion 100 1 Oral 0.00009 30 330,000 3

Turf – General High-Contact 

Activities 100 1

 Dermal 0.1410 30 210 4

Note:

1

 Target MOE= 100, Developmental rat-severe maternal clinical toxicity. NOAEL=30 

2

 MOE food = [(short-term oral NOAEL)/(chronic dietary exposure)] 3

 MOE oral = [(short -term oral NOAEL)/(hand-to-mouth residential exposure)] 

4

 MOE dermal = [(short -term dermal NOAEL)/(high-end dermal residential exposure)] 5

 Aggregate Combined MOE (food, water, and residential) = 1÷ [(1÷MOE food and water) + (1÷MOE oral) + 

(1÷MOE dermal)]. 

Table 6.2.2 aggregates the short-term risk for adults from residential postapplication, and 

average food and water (as a background). Based on the low vapor pressure of propiconazole, 

no postapplication inhalation exposure is anticipated to occur. No postapplication exposures are 

expected to occur with antimicrobial uses. The highest postapplication exposure from residential 

use on turf was used in the short-term aggregate. The aggregate MOE is 320, which is greater 

than the target MOE of 100. This aggregate exposure assessment is considered very 

conservative because the assumptions used for each of the scenarios separately are already high 

end (i.e., time spent outdoors, dislodgeable residues). 
Page 27 of 31 

Table 6.2.2. Short-term Aggregate Risk Estimates to Propiconazole for Adults from Postapplication Activities

Exposure Scenario 

Target 

MOE Route of 

Exposure 

Exposure 

Or 

Daily dose 

NOAELs MOE at Day 0 Combined MOE4

Average Food and Water 

(As background) 

N/A Food and 

water 0.0068 30 4400 2

320 Residential Postapplication 

(Residential Turf Gen. HighContact Activities)) 100 1

 Dermal 0.085 30 350 3

Note:

1

 Target MOE= 100, Developmental rat- increased incidence of rudimentary risks. NOAEL = 30 2

 MOE food and water = [(short-term oral NOAEL)/(chronic dietary exposure)] 

3

 MOE dermal = [(short -term dermal NOAEL)/(high-end dermal residential exposure)] 4

 Aggregate Combined MOE (food, water, and residential) = 1÷ [(1÷MOE food and water) + (1÷MOE post appl. 

dermal)]. 

6.3 Intermediate-Term Aggregate Risk 

The only residential use scenario that will result in potential intermediate-term exposure to 

propiconazole is postapplication exposure to Children from wood treatment (antimicrobial use). 

Table 6.3 shows the aggregate risk for intermediate-term exposure to Children 1-2 years old. 

The aggregate MOE is 110, which is greater than the target MOE of 100. 

Table 6.3. Intermediate -term Aggregate Risk Estimates to Propiconazole for Toddler (Children 1-2years)

Exposure Scenario 

Target 

MOE Route of 

Exposure Exposure NOAELs MOE at Day 0 Combined MOE5

Average Food and Water 

(As background) 

N/A Food and 

water 0.0182 10 550 2

110 

Incidental oral 100 1 Oral 0.0056 10 18003

Dermal Contact Activities 100 1 Dermal 0.068 10 150 4

Note:

1

 Target MOE= 100, 24 Month oncogenicity study. NOAEL=10 

2

 MOE food = [(intermediate-term oral NOAEL)/(chronic dietary exposure)] 3

 MOE oral = [(intermediate -term oral NOAEL)/(hand-to-mouth residential exposure)] 4

 MOE dermal = [(intermediate -term dermal NOAEL)/(high-end dermal residential exposure)] 

5

 Aggregate Combined MOE (food, water, and residential) = 1÷ [(1÷MOE food and water) + (1÷MOE oral) + 

(1÷MOE dermal)]. 

6.4 Long-Term Aggregate Risk 

Since there are no residential uses that will likely result in chronic exposure to propiconazole, 

chronic aggregate includes food and water only. Water exposure has been included in the 

DEEM analysis; therefore, the result of chronic aggregate risk assessment is as shown in Table 
Page 28 of 31 

4.3. Propiconazole does not possess a separate cancer dietary endpoint—the RfD approach is 

considered protective; therefore, the results of only the acute and chronic analyses are given. 

7.0 CUMULATIVE RISK CHARACTERIZATION/ASSESSMENT

Propiconazole is a member of the triazole-derivative fungicide class of pesticides. Although 

triazole-derivative fungicides act similarly in plants (fungi) by inhibiting ergosterol biosynthesis, 

there is not necessarily a relationship between their pesticidal activity and their mechanism of 

toxicity in mammals. Structural similarities do not constitute a common mechanism of toxicity. 

Evidence is needed to establish that the chemicals operate by the same, or essentially the same, 

sequence of major biochemical events (EPA, 2002). In triazole-derivative fungicides, however, 

a variable pattern of toxicological responses is found. Some are hepatotoxic and 

hepatocarcinogenic in mice. Some induce thyroid tumors in rats. Some induce developmental, 

reproductive, and neurological effects in rodents. Furthermore, they produce a diverse range of 

biochemical events including altered cholesterol levels, stress responses, and altered DNA 

methylation. It is not clearly understood whether these biochemical events are directly 

connected to their toxicological outcomes. Thus, there is currently no evidence to indicate that 

triazole-derivative fungicides share common mechanisms of toxicity and EPA is not following a 

cumulative risk approach based on a common mechanism of toxicity for the these pesticides. 

For information regarding EPA’s procedures for cumulating effects from substances found to 

have a common mechanism of toxicity, see EPA’s website at 

http://www.epa.gov/pesticides/cumulative.

Propiconazole, like other triazole-derivative fungicides, can form the common metabolites 1,2,4-

triazole and its triazole conjugates (triazolylalanine, triazolylacetic acid, and triazolylpyruvic 

acid). To support existing tolerances and to establish new tolerances for triazole-derivative 

pesticides, including propiconazole, U.S. EPA conducted a human health risk assessment for 

exposure to 1,2,4-triazole, triazolylalanine, triazolylacetic acid and triazolylpyruvic acid 

resulting from the use of all current and pending uses of any triazole-derivative fungicide. The 

risk assessment is a highly conservative, screening-level evaluation in terms of hazards 

associated with common metabolites (e.g., use of a maximum combination of uncertainty 

factors) and potential dietary and non-dietary exposures (i.e., high end estimates of both dietary 

and non-dietary exposures). In addition, the Agency retained the additional 10X FQPA safety 

factor for the protection of infants and children. The assessment includes evaluations of risks for 

various subgroups, including those comprised of infants and children. The Agency’s complete 

risk assessment is found in the propiconazole reregistration docket at 

http://www.regulations.gov, Docket Identification (ID) Number EPA-HQ-OPP-2005-0497. 
Page 29 of 31 

8.0 OCCUPATIONAL EXPOSURE AND RISK

For a detailed discussion refer to: Section 18 Emergency Exemption for Propiconazole (Tilt EPA Reg. No. 100-

617); for Use on Avocado Trees; HED memo by J. Miller, D380160, 7/28/10. 

8.1 Occupational Handler 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) Version 1.1. 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 exposures 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. 

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. 

For propiconazole a Q1* for carcinogenicity was not established and the RfD approach is 

considered protective; therefore, a cancer risk assessment for handlers is not required. 

The resulting doses and MOEs are presented in Table 8.1. 
Page 30 of 31 

Table 8.1. 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) acres 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 
Page 31 of 31 

8.2 Occupational Postapplication Exposure and Risk

Based on the use patterns associated with the proposed Section 18 label, HED believes that 

postapplication exposure will be negligible. Therefore, a postapplication quantitative assessment 

was not conducted. 

9.0 REFERENCES

1) Section 18 Drinking Water Assessment; EFED memo by J. Lin (D379850, 07 /15/10). 

2) Section 18 Propiconazole Dietary Exposure and Risk Assessment; HED memo by T. 

Morton (D380158, 07/21/10). 

3) Section 18 Common Triazole Metabolites Updated Dietary Exposure and Risk 

Assessment; HED memo by T. Morton (D380341, 7/27/10). 

4) Section 18 Occupational and Residential Exposure Assessment; HED memo by J. Miller 

(D380160, 07/28/10). 

5) Propiconazole – Fifth Carcinogenicity Peer Review; E. Doyle and E. Rinde (TXR 

0009771, 9/11/92). 

6) Propiconazole- 3rd Report of the Hazard Identification Assessment Review Committee; J. 

Kidwell (TXR 0052277, 12/17/03). 

7) Propiconazole Occupational and Residential Exposure Assessment of the Antimicrobial 

Uses; T. Leighton (D326306, 2/1/2006). 

8) Amendment to the Propiconazole RED for Children’s Postapplication Exposure from 

Treated Structures; T. Leighton (D330159, 06/20/06). 

9) Propiconazole: Revised Occupational and Residential Exposure Assessment; HED memo 

by J. Miller (D329393, 6/15/06). 

10) Reregistration Eligibility Decision (RED) for Propiconazole; July 2006. 

11) HED re-registration eligibility document (RED) for Propiconazole; HED memo by Y. 

Donovan (D329668, 6/28/06). 

12) Propiconazole FQPA Human Health Risk Assessment for the Section 3 Registrations on 

Garden Beets, Turnips, Parsley, Cilantro and Pineapple; HED memo by Y. Donovan 

(D347905, 9/30/08). 

13) Propiconazole (Tilt) in or on Wild Rice and Stone Fruit. Evaluation of Residue Data and 

Analytical Methods; HED memo by S. Malak (MRID 41063802; PP#9F3758; No DP 

Barcode #, 11/28/89).