Page 3 of 53

A.2 Toxicity Profiles............................................................................45

Appendix B: EPA Review of Human Research ...................................................................... 51

Appendix C: Physical and Chemical Properties ..............................................................52

Appendix D: International Residue Limit Status....................................................................52

Appendix E: Chemical Names and Structures of Metabolites.....................................53
Page 4 of 53

1.0 EXECUTIVE SUMMARY

This assessment provides information to support a Section 3 registration for the use of 

propiconazole on dry and succulent beans, and addition of post-harvest uses on citrus, stone fruit, 

and tomato. This document addresses risks associated with exposures from currently registered 

uses as well as the proposed new uses of propiconozole. It also assesses potential enhanced 

sensitivity of infants and children from dietary and/or residential exposure as required under the 

Food Quality Protection Act (FQPA) of 1996.

Use Profile

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

is a systemic triazole-type fungicide that provides broad spectrum disease control on a variety of 

food and non-food crops. Permanent tolerances are established (40 CFR §180.434) for the 

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

(2,4-DCBA)) in/on a variety of agricultural commodities at levels ranging from 0.05 ppm in/on 

meat and meat byproducts to 40 ppm in/on grass straw. Non-food uses include use on 

commercial, public and residential ornamentals, landscapes and turf. The mode of antifungal 

action of propiconazole is attributed to the inhibition of CYP51 (lanosterol-14-a-demethylase). 

Inhibition of normal sterol production disrupts cell wall formation and slows or stops the growth 

of the fungus. Agricultural applications of propiconazole are made using ground or aerial

equipment. Propiconizole is applied to non-food areas by both occupational and residential 

handlers. Occupational application methods for non-food uses include, seed piece dip, tree 

injection, and handheld equipment (i.e., low-pressure handwand, handgun sprayer, backpack 

sprayer). Residential applications are made with handheld equipment. 

Proposed New Uses

The Interregional Research Project No. 4 (IR-4) has submitted an application for the registration 

of products containing propiconazole for use on dry beans, snap beans, succulent shelled beans, 

and post-harvest use on citrus fruit, stone fruit, and tomato. The products are manufactured by 

Syngenta Crop Protection, Inc. under the trade name Tilt®Fungicide (EPA Reg. No. 100-617), 

Quilt®Fungicide (EPA Reg. No. 100-1178), Quilt Xcel®Fungicide (EPA Reg. No. 100-1324)

and Tilt 45W®Fungicide (EPA Reg. No. 100-780) . A 7 day PHI is proposed for dry beans and 

a 0 day PHI is proposed for succulent beans. The new product is not proposed for residential use 

and residential exposures are not expected based on the proposed uses. 

Hazard Identification

The toxicology database for propiconazole is adequate for evaluating and characterizing toxicity 

and selecting endpoints for purposes of this risk assessment. The primary target organ for 

propiconazole toxicity in animals is the liver. Liver effects observed in subchronic and chronic 

oral studies in rats and mice include lesions, hypertrophy and necrosis. Propiconazole is not a 

reproductive toxicant. In a rat developmental study, fetal effects in pups were observed at doses 

lower than doses at which maternal effects were seen providing quantitative evidence of 
Page 5 of 53

increased susceptibility of fetuses to in utero exposure to propiconozole. Propiconozole does not 

appear to be neurotoxic based on an acute neurotoxicity study. The FQPA safety factor was 

reduced to 1X because residual uncertainties with regard to pre- and/or postnatal toxicity are 

minimal. 

Propiconazole is classified as a Group C possible human carcinogen with risk quantitated using a 

reference dose (RfD) approach. Propiconazole showed no significant toxicity in a battery of 

acute toxicity tests (Toxicity Category III or IV in all tests). It is not a skin irritant but is a 

dermal sensitizer. Immunotoxicity and subchronic neurotoxicity studies are required as part of 

new 40 CFR Part 158 requirements for registration of a pesticide. 

Dose Response Assessment

Toxicological endpoints were selected for dietary/drinking water, occupational and residential 

exposure scenarios. Acute and chronic Population Adjusted Doses (PADs) were selected for 

assessment of food and drinking water exposures. An acute PAD for the general population was

selected from an acute neurotoxicity study in rats. An acute PAD for females 13-49 was selected 

from a developmental toxicity study in rats. A chronic/cancer PAD for the general population 

was selected from a carcinogenicity study in mice. Short and intermediate-term occupational 

exposures via the dermal and inhalation routes may occur based on the use pattern and label 

directions. Toxicological endpoints for inhalation, dermal, and incidental oral exposures were

selected from the acute neurotoxicity study in rats. Since an oral study was selected for dermal 

exposure, a 40% dermal absorption factor from a dermal absorption study in rates is used for 

route to route extrapolation. An uncertainty factor of 100X was applied to endpoints selected for 

all exposure routes (10x for interspecies extrapolation, 10x for intraspecies variation). 

Exposure/Risk Assessment and Risk Characterization

Risk assessments were conducted for dietary (food and water), and occupational exposure 

pathways based on registered uses and requests for new uses of propiconazole. Worker

exposures were assessed for handler and post-application activities. There are no new requested 

residential uses expected with this registration, therefore residential risk was not assessed for the 

proposed new use. Conservative acute and chronic dietary and drinking water risk assessments 

for propiconazole conclude that dietary and drinking water exposure estimates are below HED‘s 

level of concern for the general population and all population subgroups. Additionally, the 

requested uses of propiconazole resulted in an increase in dietary exposure estimates for free 

triazole or conjugated triazoles. Therefore, dietary exposure analyses for the triazole metabolites 

needed to be updated (T. Morton, D397591, 1/26/12). Aggregate risks from propiconazole are 

not of concern. Occupational exposure and risk estimates indicate that worker and residential 

handler and post-application exposures are not of concern at the maximum allowable application

rates for the proposed new uses provided that handlers wear chemical resistant gloves as required 

on the label. The only residential use scenario that will result in potential intermediate term 

exposure to propiconazole is post application exposure to children from wood treatment 

(antimicrobial use). Table 17 shows the aggregate risk for intermediate term exposure to 

Children 1-2 years old. The aggregate MOE is 74, which is less than the target MOE of 100. 
Page 6 of 53

However, a refined chronic food and water exposure results in an MOE >100. Therefore, this 

scenario is not of concern.

Aggregate Assessment of Free Triazole & its Conjugates

The addition of the new proposed uses increase the aggregate exposure to free triazoles and its 

conjugates. Therefore, the aggregate human health risk assessment was updated for free 

triazoles and its conjugates and the aggregate estimates remain below HED‘s level of concern.

Use of Human Studies

This risk assessment relies in part on data from studies in which adult human subjects were 

intentionally exposed to a pesticide or other chemical. These studies, listed in Appendix 2.0, 

have been determined to require a review of their ethical conduct. Some of these studies are also 

subject to review by the Human Studies Review Board. All of the studies used have received the 

appropriate review.

Environmental Justice

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

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

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

http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf).

As a part of every pesticide risk assessment, OPP considers a large variety of consumer 

subgroups according to well-established procedures. In line with OPP policy, HED estimates 

risks to population subgroups from pesticide exposures that are based on patterns of that 

subgroup‘s food and water consumption, and activities in and around the home that involve 

pesticide use in a residential setting. Whenever appropriate, non-dietary exposures based on 

home use of pesticide products and associated risks for adult applicators and for toddlers, youths, 

and adults entering or playing on treated areas postapplication are evaluated. Further 

considerations are currently in development, as OPP has committed resources and expertise to 

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

farm workers as well as lifestyle and traditional dietary patterns among specific subgroups. 
Page 7 of 53

Tolerance Recommendation

Pending submission of a revised Section F (see requirements under Proposed Tolerances) and 

revised Section B (see requirements under Data Deficiencies), there are no residue chemistry 

issues that would preclude granting conditional Section 3 registration for the requested use of 

propiconozole on dry and succulent beans, and addition of post-harvest uses on citrus, stone 

fruit, and tomato, or establishment of the following tolerances for residues of propiconozole. 

Bean, snap.......................................................................... 0.70 ppm

Bean, succulent shelled...................................................... 0.10 ppm

Legume, foliage .................................................................... 30 ppm

Bean, dry seed.................................................................... 0.40 ppm

Tomato ................................................................................. 3.0 ppm

Fruit, citrus, group 10-10 ..................................................... 8.0 ppm

Fruit, stone, group 12, except plum ..................................... 4.0 ppm

Plum................................................................................... 0.60 ppm

Citrus oil............................................................................ 1000 ppm

As previously noted, permanent tolerances are currently established for the combined residues of 

propiconazole and its 2,4-DCBA containing metabolites at levels ranging from 0.1-40 ppm in/on 

plant commodities [40 CFR §180.434(a)]. However, HED has determined that the current 

tolerance expression should be amended to include only propiconazole per se because 1) there 

are a number of pesticides that have 2,4-DCBA as common metabolite, and an enforcement 

agency may not be able to determine if residues are due to misuse of propiconazole or the proper 

use of other pesticides containing 2,4-DCBA; 2) propiconazole per se can be detected by FDA 

multiresidue methods; and 3) inclusion of only parent allows harmonization with the residue 

definition for the Codex MRLs.

HED has determined that the current tolerance expression for plant and livestock commodities is 

not appropriate and has previously recommended that the tolerance expression be revised to 

include only parent.

Codex has established several maximum residue limits (MRLs) for propiconazole in/on various 

raw agricultural commodities. The Codex MRLs are expressed in terms of propiconazole per se, 

which is the same as the US tolerance expression. Both Canada and Mexico have established 

MRLs/tolerances on several commodities which also have U.S. tolerances. To the extent 

possible, U.S. tolerances have been harmonized with Codex, Canadian, and Mexican MRLs.

2.0 Regulatory Conclusions and Recommendations

HED can recommend for a unconditional registration and permanent tolerances for the proposed 

uses of propiconazole. Deficiencies are outlined in Section 2.1 below. The specific tolerance 

recommendations are discussed in Section 2.2, and label modifications are discussed in Section 

2.3.
Page 8 of 53

2.1 Data Deficiencies/Conditions of Registration

Note to PM:

Revised Section F required.

Revised Section B required. A 0-day PHI is proposed for succulent beans. However, 

residue data were submitted for 5-8 day PHI. Therefore, the label must be amended to 

state a 7 day PHI for succulent beans.

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

An adequate method, HPLC/UV Method AG-671A, is available for tolerance enforcement. This 

method has undergone a successful tolerance method validation by the Analytical Chemistry 

Branch of BEAD. The method was forwarded to FDA for inclusion in PAM Volume II. This 

method has an LOQ of 0.02 ppm. The method includes optional detection via HPLC/MS, giving 

a means of residue confirmation. 

2.2.2 International Harmonization

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

for propiconazole in/on various raw agricultural commodities. The Codex MRLs are expressed 

in terms of propiconazole per se, which is the same as the US tolerance expression, 

recommended by the RED for existing tolerances and for the new uses. In addition, both Canada 

and Mexico have established MRLs/tolerances on several commodities which also have U.S. 

tolerances. To the extent possible, U.S. tolerances have been harmonized with Codex, Canadian, 

and Mexican MRLs.

2.2.3 Recommended Tolerances

The proposed use and the submitted data support the following tolerances for residues of 

propiconazole on/on the following raw agricultural commodities.

Bean, snap.......................................................................... 0.70 ppm

Bean, succulent shelled...................................................... 0.10 ppm

Legume, foliage .................................................................... 30 ppm

Bean, dry seed.................................................................... 0.40 ppm

Tomato ................................................................................. 3.0 ppm

Fruit, citrus, group 10-10 ..................................................... 8.0 ppm

Fruit, stone, group 12, except plum ..................................... 4.0 ppm

Plum................................................................................... 0.60 ppm

Citrus oil............................................................................ 1000 ppm
Page 9 of 53

2.2.4 Revisions to Petitioned-For Tolerances

IR-4 has submitted a petition, PP#1E7855, for the establishment of tolerances for the combined 

residues of the fungicide 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 and 

expressed as parent compound, in or on the following commodities:

Bean, snap............................................................................ 0.8 ppm

Bean, succulent shelled...................................................... 0.15 ppm

Legume, foliage .................................................................... 25 ppm

Bean, dry seed...................................................................... 0.3 ppm

Tomato ................................................................................. 2.5 ppm

Fruit, citrus, group 10-10 ..................................................... 8.0 ppm

Fruit, stone, group 12, except plum ..................................... 7.0 ppm

Plum..................................................................................... 1.0 ppm

HED has concluded that the residues of concern should include propiconazole and all its 

metabolites containing the 2,4-DCBA moiety, including conjugates for dietary risk assessment of 

food, as virtually all the residue data have been generated using a common moiety method that 

converts parent and all of the metabolites of concern to 2,4-DCBA. The tolerance expression 

should also be amended to include only propiconazole per se because 1) there are a number of 

pesticides that have 2,4-DCBA as common metabolite, and an enforcement agency may not be 

able to determine if residues are due to misuse of propiconazole or the proper use of other 

pesticides containing 2,4-DCBA; 2) propiconazole per se can be detected by FDA multiresidue 

methods; and 3) inclusion of only parent allows harmonization with the residue definition for the 

Codex MRLs. The tolerance expression for propiconazole in 40 CFR §180.434(a)(1) should be 

stated according to HED‘s Interim Guidance on Tolerance Expression (5/27/09, S. Knizer) as 

specified in Section 2.2.3.

Adequate crop field trial data reflecting the proposed use patterns were submitted for purposes of 

establishing tolerances on the requested new uses. The Organization for Economic Cooperation 

and Development tolerance calculation procedures were utilized in determining the appropriate 

tolerance level for the requested new uses. Changes in recommended tolerances are based on the 

use of these calculation procedures and are shown in Table 1.

The highest average field trial (HAFT) residue from the citrus field trials is 4.91 ppm. This 

residue multiplied by the processing factor for dried citrus pulp (4.91 X 1.4) yields 6.9 ppm. As 

this is less than the recommended tolerance for citrus, at 8.0 ppm, no separate tolerance for is 

necessary. When the HAFT is multiplied by the processing factor for citrus oil (4.91 X 185) the 

final residue is 908 ppm. Therefore, a tolerance for citrus oil should be proposed at 1000 ppm.

The proposed and recommended tolerances for propiconazole as a result of the subject action are 

presented in Table 1.
Page 10 of 53

Table 1. Tolerance Summary for Propiconazole.

Commodity Proposed Tolerance

(ppm)

Recommended Tolerance

(ppm) Comments

40 CFR §180.434(a)(1)

Bean, snap 0.8 0.70

Bean, succulent shelled 0.15 0.10

Legume, foliage 25 30

Bean, dry seed 0.3 0.40

Tomato 2.5 3.0

Fruit, citrus, group 10-10 8.0 8.0

Fruit, stone, group 12, 

except plum 7.0 4.0

Plum 1.0 0.60

Citrus oil none 1000 Tolerance needed based on, 

HAFT x processing factor

*Changes are due to the use of the Organization for Economic Cooperation and Development tolerance calculation 

procedures, unless otherwise stated.

2.3 Label Modifications

A 0-day PHI is proposed for succulent beans. However, residue data were submitted for 5-8 day 

PHI. Therefore, the label must be amended to state a 7 day PHI for succulent beans.

3.0 Ingredient Profile

3.1 Summary of Proposed Uses

Propiconazole is proposed for use on dry beans, snap beans, succulent shelled beans, and 

post-harvest use on citrus, stone fruit, and tomatoes. (Table 2). 
Page 11 of 53

Table 2. Proposed Amended Uses of Propiconazole (Fungicide)

Product 

(EPA Reg. No.) Use Site Appl. Method

Application Rate 

Range

(lb ai/A)

Comments

Tilt®

(100-6177)

41.8%

3.6 lbs ai/gal

Beans, 

Group 06

Ground, 

Aerial, 0.1125

Fungicide. Up to three applications may be made on 

a 7-14 day interval. Do not apply more than 12 oz. 

of Tilt / crop /Acre. 7 day PHI

Quilt XcelTM 

(100-1324) 

11.7% 

1.02 lbs ai/gal

Ground, 

Aerial 0.084 - 0.114

Up to three applications may be made on a 7-14 day 

interval. Not for use on cowpea intended for 

livestock feeding only. Do not apply more the 42 oz. 

of product/crop/A. Do not apply more than 0.34 lb 

ai of propiconazole containing products. 7 day PHI.

QuiltTM 

(100-1178) 

11.7% 

1.04 lbs ai/gal

Ground, 

Aerial 0.114

Up to three applications may be made on a 7-14 day 

interval. Do not apply more than 42 oz. of 

product/crop/Acre. Do not apply more than 0.34 lb 

ai of propiconazole containing products. 7 day PHI

Product 

(EPA Reg. No.) Use Site App. Method

App. Rate Range 

(lb. a.i./ gal) 

or 

(lb a.i. / # lbs. fruit)

Comments

Tilt® 45W

(100-780)

45%

Wettable Powder

Tomato, 

Group 8

In-line 

Dip/Drench

 

0.00113 - 0.00225 

(lb ai / gal)

Use T-Jet, CDA or similar application system. 

Must be used in tank mixture with fludioxonil. May 

be used with a food grade equivalent. 

 

Dip approximately 30 seconds and allow fruit to 

drain. Must be used in tank mixture with 

fludioxonil. May be used with a food grade 

equivalent

Aqueous or 

Fruit Coating 

Spray 

Application

 

(0.113 – 0.225 lb a.i.

/50,000 lbs. of Fruit)

Citrus, 

Group 10

In-line 

Dip/Drench

0.00225 - 0.0045 

(lb ai / gal)

Aqueous or 

Fruit Coating 

Spray 

Application

(0.225 – 0.45 

lba.i./250,000 lbs. of

Fruit)

Stone Fruit 

(Group 12)

In-line 

Dip/Drench 

In-line

0.000563 - 0.00113 

(lb ai/gal)

Aqueous or 

Fruit Coating 

Spray 

Application

 

(0.056 – 0.113 lb 

a.i./250,000 lbs. of 

Fruit)
Page 12 of 53

3.2 Structure and Nomenclature

Structure and nomenclature are reported in Table 3.

Table 3. Nomenclature of Propiconazole

Compound

N

N N

O

O

Cl

Cl

Common name Propiconazole

Company experimental names CGA-64250

IUPAC name 1-[2-(2,4_dichlorophenyl)-4-propyl-1,3-dioxolan-2-ylmethyl]-1H-1,2,4_triazole

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

CAS # 60207-90-1

End-use products/EP 3.6 lb/gal EC (EPA Reg. Nos. 100-617 

3.3 Physical and Chemical Properties

The physicochemical properties of propiconazole are reported in Appendix C. 

3.4 Anticipated Exposure Pathways

The Registration Division has requested an assessment of human health risk to support the 

proposed new uses of propiconazole on dry beans, snap beans, succulent shelled beans, and 

postharvest use on citrus fruit, stone fruit and tomato. For domestic uses, humans may be 

exposed to propiconazole in food and drinking water, since propiconazole may be applied 

directly to growing crops and application may result in propiconazole reaching surface and 

ground water sources of drinking water. In an occupational setting, applicators may be exposed 

while handling the pesticide prior to application, as well as during application. There is a 

potential for post-application exposure for workers re-entering treated fields. There are also 

residential uses of propiconazole, so there is exposure in residential or non-occupational settings.

Risk assessments have been previously prepared for the existing uses of propiconazole. This risk 

assessment considers all of the aforementioned exposure pathways based on the proposed new 

uses of propiconazole, but also considers the existing uses as well, particularly for the dietary 

exposure assessment.

3.5 Consideration of Environmental Justice

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

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

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

http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf.
Page 13 of 53

As a part of every pesticide risk assessment, OPP considers a large variety of consumer 

subgroups according to well-established procedures. In line with OPP policy, HED estimates 

risks to population subgroups from pesticide exposures that are based on patterns of that 

subgroup‘s food and water consumption, and activities in and around the home that involve 

pesticide use in a residential setting. Extensive data on food consumption patterns are compiled 

by the USDA under the Continuing Survey of Food Intake by Individuals (CSFII) and are used 

in pesticide risk assessments for all registered food uses of a pesticide. These data are analyzed 

and categorized by subgroups based on age, season of the year, ethnic group, and region of the 

country. Additionally, OPP is able to assess dietary exposure to smaller, specialized subgroups 

and exposure assessments are performed when conditions or circumstances warrant. Whenever 

appropriate, nondietary exposures based on home use of pesticide products and associated risks 

for adult applicators and for toddlers, youths, and adults entering or playing on treated areas 

post-application are evaluated. Further considerations are currently in development as OPP has 

committed resources and expertise to the development of specialized software and models that 

consider exposure to bystanders and farm workers as well as lifestyle and traditional dietary 

patterns among specific subgroups.

4.0 Hazard Characterization/Assessment

4.1 Hazard and Dose-Response Characterization

4.1.1 Database Summary

The toxicological database for propiconazole is adequate for the purpose of this risk assessment.

A recent risk assessment document (HED memoranda B. Daiss, 04/27/11, DP389194) contains

detailed and up-to-date discussions of the toxicology and hazard evaluation of propiconazole. 

Please refer to these documents for further extensive details. Also, please refer to Appendix 2 of 

this current risk assessment document for the toxicity profile tables.

4.1.2 Studies Available and Considered

The following data are available:

Acute- Oral rat, dermal rat, inhalation rat, eye irritation rabbit, dermal irritation rabbit, and skin 

sensitization guinea pig.

Subchronic- Oral 90-day rat, oral 90-day mouse (3), and oral 90-day dog;

Chronic- Oral rat and dog;

Reproductive/developmental- Oral developmental rabbit and rat, 2-generation reproductive rat

Other- Oral rat and mouse cancer studies, 21-day dermal rabbit toxicity and dermal penetration 

study, neurotoxicity, metabolism, mutagenicity screens and mechanistic studies (3).

4.1.3 Sufficiency of Studies/Data

The toxicity database for propiconazole is adequate for the purpose of this risk assessment (see 

Appendixes for Toxicity Profile tables). 
Page 14 of 53

4.1.4 Toxicological Effects

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. 

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. Decreased body weight gain was also seen in subchronic, chronic, developmental and 

reproductive studies in animal studies. Mice appear to be more susceptible to propiconazole 

toxicity than rats. Dogs appeared to be more sensitive to the localized toxicity of propiconazole 

as manifested by stomach irritations 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 (malformations of the lung and kidneys, incomplete ossification of the skull, caudal 

vertebrae and digits, extra rib (14th rib) and missing sternbrae,) 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. 

Propiconazole was negative for mutagenicity in the in vitro BALB/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. It caused proliferative 

changes in the rat liver with or without pretreatment with an initiator, like phenobarbital, a 

known liver tumor promoter. Liver enzyme induction studies with propiconazole in mice 

demonstrated that propiconazole is a strong phenobarbital type inducer of xenobiotic 

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

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

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

4.1.5 Cancer Classification

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. 009771, April 15, 1992 meeting).
Page 15 of 53

4.2 Absorption, Distribution, Metabolism, Excretion (ADME)

The rat metabolism study labeled with 14C at the triazole-[3,5] position indicated that parent 

compound was extensively metabolized. An intravenous study labeled with (U14C)-Phenyl 

found several metabolites, including CGA 118245 (61.8% in males, 2.4% in females), CGA 

217495 (8.9% in males, 58.3% in females), CGA 91304 (2.3% in males only), and CGA 118244 

(3.6% in females only). No parent material was detected in the feces in the iv group. The 

metabolites seen in the iv study were detected to varying degrees in the urine and the feces of the 

orally dosed groups. Radiolabeled materials CGA 91305, CGA 118245 and CGA 177291 were 

reported ranging from 0.5% - 10.9% of the fecal radioactivity in males and females or in one sex 

alone. Most of the fecal radioactivity was not characterized. Metabolites CGA 217495 and 

CGA 177291 are not found in plant or livestock metabolism (see Appendix for structures). In 

two other (U14C)-phenyl and 14C-triazole ring labeled propiconazole studies, the percentages of 

fecal metabolites extracted and distributed at various pH‘s were not substantially different 

between the triazole and phenyl labeled samples, which suggest that the bridge between the 

phenyl ring and the triazole ring remained intact. The proposed metabolic pathway appears to 

involve the cleavage of the dioxolane ring through the oxidation of the propyl side chain, with 

subsequent dechlorination and conjugation. In a (U14C)-phenyl labeled propiconazole 

metabolism study in mice, it was concluded that the major metabolic pathway in mice proceeds 

via elimination of the dioxolane ring leading to ketone formation (CGA 91304) and reduction to 

yield the corresponding alcohol (CGA 91305). Both CGA 91304 and CGA 91305 are found in 

plants and livestock. 

4.3 FQPA Considerations

The toxicology database used to assess pre- and post-natal exposure to propiconazole is 

considered adequate. 

4.4 FQPA Safety Factor for Infants and Children

For propiconazole there are acceptable developmental toxicity studies in the rat and rabbit and an

acceptable multi- generation reproduction study in the rat. An acceptable acute neurotoxicity 

study in the rat is also available in the database. Subchronic neurotoxicity and immunotoxicity 

studies are required under 40 CFR Part 158 as a part of the new data requirements for 

registration of a pesticide (food and non-food uses). Although quantitative susceptibility was 

observed in the rat developmental study, a clear NOAEL. is established for the developmental 

effects. Furthermore, the acute dietary for females 13-49 years old is based on the 

developmental NOAEL from the study with quantitative susceptibility. Therefore, the risk 

assessment is protective of this susceptibility and there are no remaining uncertainties for the 

young. Together, the available data support the reduction of the FQPA factor to 1X.
Page 16 of 53

4.5 Hazard Identification and Toxicity Endpoint Selection

Doses and endpoints were selected for exposure routes (i.e., oral, dermal and inhalation) 

depending upon the appropriateness of the endpoint and the relevancy of the endpoints to the 

population of concern. Developmental (in utero exposure) endpoints were selected to assess 

dietary risks for Females 13-49 years of age, whereas non-developmental (systemic toxicity) 

endpoints were selected to assess dietary and non-occupational (residential) risks to the general 

population, including children and infants.

A summary of toxicological endpoints for use in human health risk assessment is presented 

below:

Table 4. Summary of Toxicological Doses and Endpoints for Propiconazole for Use in Dietary Human Health Risk 

Assessments

Exposure/Scenario Point of 

Departure

Uncertainty/FQP

A Safety Factors

RfD, PAD, LOC 

for Risk 

Assessment

Study and Toxicological Effects

Acute Dietary 

(General 

Population)

NOAEL = 

30

mg/kg/day

UFA= 10x

UFH=10x

FQPA SF= 1x

Acute RfD = 0.3

mg/kg/day

aPAD = 0.3

mg/kg/day

Acute neurotoxicity study Rat 46604601

LOAEL = 100 mg/kg/day based on clinical signs 

of toxicity (piloerection in one male, diarrhea in 

one female, tip toe gait in 3 females).

Acute Dietary 

(Females 13-49 

years)

NOAEL = 

30

mg/kg/day

UFA= 10x.

UFH=10x

FQPA SF= 1x

Acute RfD = 0.3

mg/kg/day

aPAD = 0.3 

mg/kg/day

Developmental Study - Rat 40425001

LOAEL = 90 mg/kg/day based on increased 

incidence of rudimentary ribs, un-ossified 

sternebrae, as well as increased incidence of 

shortened and absent renal papillae and increased 

cleft palate.

Chronic Dietary 

(Adult Males and 

Females 50+ yrs)

NOAEL = 

10

mg/kg/day

UFA= 10x

UFH=10x

FQPA SF= 1x

Chronic RfD = 

0.1

mg/kg/day

cPAD = 

0.1mg/kg/day

24-month oncogenicity study on CD-1 mice. 

00129918

LOAEL = 50 mg/kg/day based on non-neoplastic 

liver effects (increased liver weight in males and 

increase in liver lesions: masses/raised areas/ 

swellings/nodular areas mainly).

Cancer (all routes) Classification: Group C, possible human carcinogen, RfD approach for risk characterization

Point of Departure (POD) = A data point or an estimated point that is derived from observed dose-response data and used to mark the beginning 

of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL = no observed adverse effect level. 

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

potential variation in sensitivity among members of the human population (intraspecies). UFL = use of a LOAEL to extrapolate a NOAEL. UFS = 

use of a short-term study for long-term risk assessment. UFDB = to account for the absence of key date (i.e., lack of a critical study). FQPA SF = 

FQPA Safety Factor. PAD = population adjusted dose (a = acute, c = chronic). RfD = reference dose. MOE = margin of exposure. LOC = level 

of concern. N/A = not applicable
Page 17 of 53

Table 5. Summary of Toxicological Doses and Endpoints for Propiconazole for Use in Residential and Occupational 

Human Health Risk Assessments

Exposure/

Scenario

Point of 

Departure

Uncertainty 

Factors

Level of Concern 

for Risk 

Assessment

Study and Toxicological Effects

Dermal Short Term 

(1-30 days) 

DAF = 40%

NOAEL= 30

mg/kg/day

UFA= 10x

UFH=10x

Residential LOC 

for MOE = 100

Occupational LOC 

for MOE = 100

Acute Neurotoxicity Study-Rats 

LOAEL = 100 mg/kg/day based on clinical signs 

of toxicity (piloerection in one male, diarrhea in 

one female, tip toe gait in 3 females).

Dermal Intermediate 

Term (1-6 months)

DAF = 40%

NOAEL= 10

mg/kg/day 

UFA= 10x

UFH=10x

Residential LOC 

for MOE = 100

Occupational LOC 

for MOE = 100

24 Month Oncogenicity Study - Mice 

LOAEL = 50 mg/kg/day based on non-neoplastic 

liver effects (increased liver weight in males and 

increase in liver lesions: masses/raised areas/ 

swellings/nodular areas mainly).

Inhalation Short 

Term (1-30 days) 

NOAEL= 30

mg/kg/day 

UFA= 10x

UFH=10x

Occupational LOC 

for MOE = 100

Acute Neurotoxicity Study-Rats 

LOAEL = 100 mg/kg/day based on clinical signs 

of toxicity (piloerection in one male, diarrhea in 

one female, tip toe gait in 3 females).

Inhalation 

Intermediate Term

(1-6 months) 

NOAEL= 10

mg/kg/day

24 Month Oncogenicity Study - Mice 

LOAEL = 50 mg/kg/day based on non-neoplastic 

liver effects (increased liver weight in males and 

increase in liver lesions: masses/raised areas/ 

swellings/nodular areas mainly).

Cancer (all routes) Classification: Group C, possible human carcinogen, RfD approach for risk characterization

DAF = Dermal Absorption Factor 

Based on the available toxicity database and the Agency's current practices, the inhalation risk 

for propiconazole was assessed using an oral toxicity study. The Agency sought expert advice 

and input on issues related to this route to route extrapolation approach (i.e. the use of oral 

toxicity studies for inhalation risk assessment) from its Federal Insecticide, Fungicide, and 

Rodenticide Act Scientific Advisory Panel (SAP) in December 2009. The Agency received the 

SAP‘s final report on March 2, 2010 

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

process of evaluating the SAP report and may, as appropriate, reexamine and develop new 

policies and procedures for conducting inhalation risk assessments, including route to route 

extrapolation of toxicity data. If any new policies or procedures are developed, the Agency may 

revisit the need for an inhalation toxicity study for propiconazole and/or a reexamination of the 

inhalation toxicity risk assessment.

4.5.1 Recommendation for combining routes of exposure for risk assessment

When there are potential residential exposures to the pesticide, the aggregate risk assessment 

must consider exposures from three major sources: oral, dermal and inhalation exposures. There 

are potential residential post-application exposures to adults via the dermal route and to children 

via dermal and incidental oral routes of exposure. For the general population, including infants 

and children, the short term oral exposure can be aggregated with the short-term dermal and 

inhalation due to a common toxicological endpoint (clinical signs in the ACN study). A 

common toxicological endpoint was identified from the cancer mouse study for intermediate-
Page 18 of 53

and long-term oral, dermal (oral equivalent) and inhalation (oral equivalent) routes. Therefore, 

these routes can be aggregated for these scenarios for the appropriate population.

5.0 Dietary Exposure/Risk Characterization

Reference: Propiconazole. New use on Snap Beans, Succulent Shell Beans, Dry Beans, Citrus Fruit (post-harvest), 

Stone Fruit (post-harvest), and Tomato (post-harvest). T. Morton, DP389670, 1/26/12.

5.1 Pesticide Metabolism and Environmental Degradation

5.1.1 Metabolism in Primary Crops

The nature of propiconazole residues in plants is adequately understood (DP D329394, Y. 

Donovan, 6/15/06). These data indicate that the major metabolic pathway in plants involves 

hydroxylation of the n-propyl group on the dioxolane ring of the cis/trans isomers of 

propiconazole, with subsequent conjugation to sugars. A possible alternative pathway involves 

reductive deketalization of the dioxolane ring and sugar conjugation of the resulting metabolite. 

The alkyl bridge between the phenyl and triazole rings is metabolized and free 1H-1,2,4-triazole 

is released. The free triazole is readily conjugated with the amino acid, serine/alanine, forming 

triazole aniline which is further metabolized to triazole acetic acid possibly through the 

intermediate formation of triazole lactic acid. HED considers free triazole, triazole alanine, and 

triazole acetic acid to be residues of concern in plants. Since these are common metabolites from 

several triazole containing pesticides, the risk assessment for triazoles has been assessed 

separately (HED memo of 11/3/10, T. Morton, D383609).

5.1.2 Metabolism in Livestock

The nature of propiconazole residues in livestock is adequately understood based on acceptable 

goat and poultry metabolism studies (DP D329394, Y. Donovan, 6/15/06).

5.1.3 Drinking Water Residue Profile

Reference: Drinking Water Exposure Assessment for the IR-4 Petition (1E7855) that Proposes Tolerances 

Residues of Propiconazole on Dry Beans, Succulent Beans, and Snap Beans. DP389673, I. Abdel-Saheb, 1/4/12.

For propiconazole, turf, a previously registered crop, has the highest application rate (6.285 lb 

a.i./A, 8 applications of 0.786 lb a.i../A per year with a 14-day interval between applications) 

((DP 325821,328690, Dated 07/07/2006). EFED has provided EDWCs for the proposed new 

uses and has provided a comparison of these new EDWCs with the previously assessed turf use. 

The previously assessed turf EDWCs are approximately one order of magnitude higher (more 

protective), than the EDWCs for new uses and therefore, the turf EDWCs were used for the 

updated dietary risk assessment.

This drinking water assessment used surface water models PRZM/EXAMS and groundwater 

model (SCI-GROW). 
Page 19 of 53

These results are based on EDWCs for Turf (DP 325821, 328690, 07/07/2006). The proposed 

new use does not result in higher EDWCs than those estimated for turf uses. 

The 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

Drinking Water Data for Free Triazoles

Residues of 1,2,4-triazole in drinking water were provided to HED by the EFED (I. Maher, 

DP320682, 28 Feb 2006). Due to the inter-conversion between 1,2,4-triazole, triazole alanine, 

and triazole acetic acid that may occur in the environment, the residue estimates used in these 

assessments are a summation of all three residues and, therefore, represent an overestimate of 

actual concentrations of the common triazole metabolites in drinking water. The Tier II 

PRZM/EXAMS (surface water) and SCIGROW (ground water) residue estimates are 

summarized in Table 5. HED notes that there were no detects of 1,2,4-triazole in any of the 271 

water samples analyzed by PDP, with a limit of quantification of 730 parts-per-trillion (0.73 

ppb). The surface water estimates are significantly greater than those for ground water, and were 

used in the assessments for free triazole as well as the conjugated metabolites. EFED stated that 

the new metconazole uses are covered by the previous drinking water assessment for 1,2,4-

triazole (DP320682, I. Maher, 2/28/06).

Table 6. Summary of Estimated Drinking Water Concentrations of 1,2,4-Triazole.

Exposure Duration Surface Water Concentration, ppm Ground Water Concentration, ppm

Acute 0.041 0.001

Chronic 0.011 0.001

5.1.4 Food Residue Profile

Residues of Concern

Reference: Propiconazole (122101): Reregistration Eligibility Decision (RED) Document; Revised Residue 

Chemistry Considerations DP329394. Y. Donovan, 6/15/06.

A summary of the metabolites and degradates to be included in the risk assessment and tolerance 

expression are presented below in Table 7. Detailed rationale for these conclusions were 

presented in a previous document (DP329394, Y. Donovan, 06/15/06).
Page 20 of 53

Table 7. Summary of Metabolites and Degradates to be included in the Risk Assessment and Tolerance 

Expression.

Matrix For Risk Assessment For Tolerance Expression

Plants Parent plus all metabolites convertible to 2,4-

DCBA

Parent only

Rotational crop Parent plus all metabolites convertible to 2,4-

DCBA

Parent only

Livestock: Parent plus all metabolites convertible to 2,4-

DCBA

Parent only

Water Parent only N/A

Note: For all triazole-containing pesticides, the triazole-containing metabolites 1,2,4-T, TA, and TAA should also 

be included as residues of concern for risk assessment purposes only for plant and livestock commodities. Since 

these metabolites are common to the entire class of triazole-derivative fungicides and because of differential toxicity 

between the metabolites and the various parent compounds, risks associated with exposure to 1,2,4-T and to 

TA/TAA are addressed in separate risk assessment documents.

M1 = 5-[(4-chlorophenyl)methyl]-2-methoxyl-2-methyl-1-(1H-1,2,4-triazol-1-ylmethyl)-1-cyclopentanol; M11 = 5-

[(4-chlorophenyl)methoxyl]-2,2-dimethyl-1-(1H-1,2,4-triazol-1-ylmethyl)-1-cyclopentanol; M12 = 5-[(4-

chlorophenyl)methyl]-2-carboxyl-2-methyl-1-(1H-1,2,4-triazol-1-ylmethyl)-1-cyclopentanol; M31 = 

(1S*,3R*,5S*)-3-hydroxy-cis-metconazole; 1,2,4-T = 1H-1,2,4-triazole; TAA = 1H-1,2,4-triazol-1-yl acetic acid; 

TA = 2-amino-3-(1H-1,2,4-triazol-1-yl)propanoic acid.

Crop Field Trials

Field trials have submitted supporting the new uses for propiconazole. The results from these 

studies are discussed in the appropriate data evaluation report (DER) and summarized in the 

following tables. 

TABLE 8. Summary of Residue Data from Snap Bean Crop Field Trials with Propiconazole.

Commodity Analyte Total App. 

Rate

(lb ai/A)

PHI

(days)

Residue Levels (ppm)1

n Sample 

Min.

Sample 

Max.

LAFT2 HAFT2 Median Mean Std. 

Dev.

Snap beans Propiconazole 0.3370-0.350946-8 7 0.0866 0.390 0.0883 0.375 0.230 0.222 0.115

T 7 <0.01 <0.01 <0.01 <0.01 0.01 0.01 N/A3

TA 7 0.0408 0.180 0.0414 0.166 0.0853 0.0945 0.0463

TAA 7 <0.01 0.0127 0.01 0.0121 0.0100 0.0106 0.0009

1

 Except for sample min/max, values reflect per trial averages; n = no. of field trials. For calculation of median, mean, and 

standard deviation, the LOQ (0.05 ppm for propiconazole, 0.01 ppm for T and TAA, and 0.03 ppm for TA) was used for any 

results reported as <LOQ in Table C.3.

2

 LAFT = lowest-average-field-trial; HAFT = highest-average-field-trial.

3 N/A = Not applicable.

4 Three applications of approximately 0.11 lb ai/A.
Page 21 of 53

TABLE 9. Summary of Residue Data from Lima Bean Crop Field Trials with Propiconazole.

Commodity Analyte Total App. 

Rate

(lb ai/A)

PHI

(days)

Residue Levels (ppm)1

n Sample 

Min.

Sample 

Max.

LAFT2 HAFT

2 Median Mean Std. Dev.

Seed Propiconazole 0.3327-0.574446-8 5 <0.05 0.0878 0.05 0.0723 0.05 0.0545 0.010

T 5 <0.01 <0.01 <0.01 <0.01 0.01 0.01 N/A3

TA 5 0.134 0.870 0.147 0.833 0.282 0.376 0.267

TAA 5 <0.01 0.0106 0.01 0.0104 0.01 0.0101 0.0002

Foliage Propiconazole 0.3327-0.5744 6-8 5 1.83 12.8 3.36 12.4 6.29 6.67 3.73

T 5 <0.01 <0.01 <0.01 <0.01 0.01 0.01 N/A3

TA 5 <0.01 0.138 <0.01 0.0108 0.0159 0.0409 0.0466

TAA 5 <0.01 0.0291 0.0108 0.0264 0.0143 0.0171 0.0068

1

 Except for sample min/max, values reflect per trial averages; n = no. of field trials. For calculation of median, mean, and 

standard deviation, the LOQ (0.05 ppm for propiconazole, 0.01 ppm for T and TAA, and 0.02 ppm for TA) was used for any 

results reported as <LOQ in Table C.3.

2

 LAFT = lowest-average-field-trial; HAFT = highest-average-field-trial.

3 N/A = Not applicable.

4 Three applications of approximately 0.11 lb ai/A.

TABLE 10. Summary of Residue Data from Dry Bean Crop Field Trials with Propiconazole.

Commodity Analyte Total App. 

Rate

(lb ai/A)

PHI

(days)

Residue Levels (ppm)1

n Sample 

Min.

Sample 

Max.

LAFT2 HAFT2 Median Mean Std. Dev.

Dry bean 

seed

Propiconazole 0.3285-0.364145-8 12 <0.05 0.253 0.05 0.248 0.0796 0.0985 0.0593

T 12 <0.01 <0.01 0.01 0.01 0.01 0.01 N/A3

TA 12 <0.04 0.233 0.04 0.226 0.111 0.115 0.065

TAA 12 <0.01 <0.01 0.01 0.01 0.01 0.01 N/A3

1

 Except for sample min/max, values reflect per trial averages; n = no. of field trials. For calculation of median, mean, and 

standard deviation, the LOQ (0.05 ppm for propiconazole, 0.01 ppm for T and TAA, and 0.04 ppm for TA) was used for any 

results reported as <LOQ in Table C.3.

2

 LAFT = lowest-average-field-trial; HAFT = highest-average-field-trial.

3 N/A = Not applicable.

4 Three applications of approximately 0.11 lb ai/A.
Page 22 of 53

TABLE 11. Summary of Residue Data from Tomato Crop Field Trials with Propiconazole.

Commodity Treatment 

Type

Analyte Total 

App. 

Rate

lb a.i./

100 gal

DAA Residue Levels (ppm)1

n Sample 

Min.

Sample 

Max.

LAFT2 HAFT2 Median Mean Std. 

Dev.

Tomatoes (large and small)

Tomato Dip Propiconazole 

Only

0.2242-

0.2249

0 6 0.412 1.12 0.469 1.12 0.676 0.702 0.254

Drench 0.2246-

0.2249

0 3 0.394 1.50 0.457 1.38 0.865 0.901 0.463

Spray 0.2250-

0.22563

0 3 0.324 1.53 0.366 1.47 0.743 0.860 0.561

Tomato Dip Total 

Propiconazole 

(as 2,4-

DCBA, 

expressed as 

propiconazole

equivalents)

0.2242-

0.2249

0 6 0.331 1.23 0.423 1.13 0.602 0.679 0.259

Drench 0.2246-

0.2249

0 3 0.331 1.52 0.379 1.44 1.04 0.953 0.536

Spray 0.2250-

0.22563

0 3 0.284 1.76 0.324 1.51 0.715 0.850 0.604

1

 Except for sample min/max, values reflect per trial averages; n = no. of field trials. 

2

 LAFT = lowest-average-field-trial; HAFT = highest-average-field-trial.

3 The application rate was lb propiconazole/50,000 lb fruit.

4 N/A = Not applicable.

TABLE 12. Summary of Residue Data from Citrus Crop Field Trials with Propiconazole.

Commodity

Treatment 

Type

Analyte Total 

App. 

Rate

lb a.i./

100 gal5

DAA Residue Levels (ppm)1

n Sample 

Min.

Sample 

Max.

LAFT2 HAFT2 Median Mean Std. 

Dev.

Orange Dip Propiconazole 0.80405-

0.80743

0 8 0.77 5.66 0.87 4.91 2.425 2.79 1.20

Spray 0.81752-

0.827613

0 4 1.03 2.32 1.08 2.28 1.23 1.46 0.56

Grapefruit Dip Propiconazole 0.80405-

0.80768

0 2 0.90 1.44 0.92 1.31 1.12 1.12 0.28

Spray 0.8243730 1 1.19 1.41 1.30 1.30 N/A4 N/A N/A

Lemon Dip Propiconazole 0.80405 0 2 1.92 3.19 2.11 2.99 2.55 2.55 0.62

Spray 0.82131-

0.826223

0 2 0.92 1.14 0.93 1.12 1.03 1.03 0.13

1

 Except for sample min/max, values reflect per trial averages; n = no. of field trials. 

2

 LAFT = lowest-average-field-trial; HAFT = highest-average-field-trial.

3 The application rate was lb propiconazole/250,000 lb fruit.

4 N/A = Not applicable.

5 Two applications of approximately 0.4 lb ai/100 gal.
Page 23 of 53

TABLE 13. Summary of Residue Data for Propiconazole (as Propiconazole and as 2,4-DCBA) from Stone 

Fruit Crop Field Trials with Propiconazole.

Commodity Analyte1 Total App. 

Rate1 

DAA Residue Levels (ppm)2

n Sample 

Min.

Sample 

Max.

LAFT3 HAFT3 Median Mean Std. 

Dev.

TRT 02 (Peach High-Volume Spray)

Peach, Fruit Propiconazole 0.11415-0.11861 0 2 0.14 0.20 0.14 0.20 0.17 0.17 0.04

Propiconazole 

(as, 2,4-DCBA)

2 0.13 0.33 0.13 0.33 0.23 0.23 0.14

TRT 03 (Peach Low-Volume Spray)

Peach, Fruit Propiconazole 0.11365-0.11445 0 2 0.43 0.56 0.49 0.50 0.50 0.50 0.01

Propiconazole 

(as, 2,4-DCBA)

2 0.42 0.43 0.42 0.43 0.43 0.43 0.01

TRT 04 (Peach Dip)

Peach, Fruit Propiconazole 0.11252-0.11285 0 4 1.16 2.17 1.17 2.11 1.54 1.59 0.42

Propiconazole 

(as, 2,4-DCBA)

4 0.73 2.52 0.73 2.52 1.68 1.65 0.89

TRT 05 (Plum Low-Volume Spray)

Plum, Fruit Propiconazole 0.11384-0.11596 0 2 0.15 0.20 0.16 0.19 0.18 0.18 0.02

Propiconazole 

(as, 2,4-DCBA)

2 0.13 0.40 0.13 0.40 0.27 0.27 0.19

TRT 06 (Plum Dip)

Plum, Fruit Propiconazole 0.11265 0 2 0.16 0.22 0.18 0.20 0.19 0.19 0.01

Propiconazole 

(as, 2,4-DCBA)

2 0.11 0.13 0.11 0.13 0.12 0.12 0.01

TRT 07 (Cherry Dip)

Cherry, 

Fruit

Propiconazole 0.11244-0.11265 0 2 0.65 1.00 0.67 0.85 0.76 0.76 0.13

Propiconazole 

(as, 2,4-DCBA)

2 0.78 2.23 0.78 2.23 1.51 1.51 1.03

TRT 07 (Cherry High-Volume Spray)

Cherry, 

Fruit

Propiconazole 0.11208 0 1 0.16 0.17 0.17 0.17 0.17 0.17 N/A

Propiconazole 

(as, 2,4-DCBA)

1 0.24 0.24 0.24 0.24 0.24 0.24 N/A

1

Spray application rate = lb ai/200,000 lb fruit for peach and plum and lb ai/25,000 lb fruit for cherry for the packing-line 

treatment applications and lb ai/100 gal water for the dip treatment applications. 

2

 Except for sample min/max, values reflect per trial averages; n = no. of field trials. For calculation of median, mean, and 

standard deviation, the LOQ (0.05 ppm for all analytes) was used for any results reported as <LOQ in Table C.3. N/A = Not 

applicable.

3

 LAFT = lowest-average-field-trial; HAFT = highest-average-field-trial.
Page 24 of 53

TABLE 14. Summary of Residue Data for Triazole Metabolites from Stone Fruit Crop Field Trials with 

Propiconazole.

Commodity Analyte Total App. 

Rate1 

DAA Residue Levels (ppm)2

n Sample 

Min.

Sample 

Max.

LAFT3 HAFT3 Median Mean Std. 

Dev.

TRT 02 (Peach High-Volume Spray)

Peach, Fruit T 0.11415-0.11861 0 2 <0.05 <0.05 0.05 0.05 0.05 0.05 N/A

TA 2 0.06 0.06 0.06 0.06 0.06 0.06 0.00

TAA 2 <0.05 <0.05 0.05 0.05 0.05 0.05 N/A

TRT 03 (Peach Low-Volume Spray)

Peach, Fruit T 0.11365-0.11445 0 2 <0.05 <0.05 0.05 0.05 0.05 0.05 N/A

TA 2 0.06 0.09 0.07 0.08 0.08 0.08 0.01

TAA 2 <0.05 <0.05 0.05 0.05 0.05 0.05 N/A

TRT 04 (Peach Dip)

Peach, Fruit T 0.11252-0.11285 0 4 <0.05 <0.05 0.05 0.05 0.05 0.05 N/A

TA 4 0.07 1.94 0.08 1.83 0.13 0.54 0.86

TAA 4 <0.05 0.17 0.05 0.16 0.05 0.08 0.06

TRT 05 (Plum Low-Volume Spray)

Plum, Fruit T 0.11384-0.11596 0 2 <0.05 <0.05 0.05 0.05 0.05 0.05 N/A

TA 2 <0.05 0.09 0.05 0.08 0.07 0.07 0.02

TAA 2 <0.05 <0.05 0.05 0.05 0.05 0.05 N/A

TRT 06 (Plum Dip)

Plum, Fruit T 0.11265 0 2 <0.05 <0.05 0.05 0.05 0.05 0.05 N/A

TA 2 <0.05 0.08 0.05 0.08 0.07 0.07 0.02

TAA 2 <0.05 <0.05 0.05 0.05 0.05 0.05 N/A

TRT 07 (Cherry Dip)

Cherry, 

Fruit

T 0.11244-0.11265 0 2 <0.05 <0.05 0.05 0.05 0.05 0.05 N/A

TA 2 0.10 0.59 0.12 0.47 0.30 0.30 0.25

TAA 2 0.05 0.08 0.05 0.07 0.06 0.06 0.01

TRT 07 (Cherry High-Volume Spray)

Cherry, 

Fruit

T 0.11208 0 1 <0.05 <0.05 0.05 0.05 0.05 0.05 N/A

TA 1 <0.05 <0.05 0.05 0.05 0.05 0.05 N/A

TAA 1 <0.05 <0.05 0.05 0.05 0.05 0.05 N/A

1

Spray application rate = lb ai/200,000 lb fruit for peach and plum and lb ai/25,000 lb fruit for cherry for the packing-line 

treatment applications and lb ai/100 gal water for the dip treatment applications. 

2

 Except for sample min/max, values reflect per trial averages; n = no. of field trials. For calculation of median, mean, and 

standard deviation, the LOQ (0.05 ppm for all analytes) was used for any results reported as <LOQ in Table C.3. N/A = Not 

applicable.

3

 LAFT = lowest-average-field-trial; HAFT = highest-average-field-trial.

Processed Food and Feed

The submitted citrus processing study is acceptable. Processing of the orange RAC with 

quantifiable residues of propiconazole resulted in the concentration of residues in dried pulp 

(1.4x processing factor) and oil (185x processing factor), but not in juice (<0.01x processing 

factor). The observed concentration factors were less than the theoretical concentration factors.
Page 25 of 53

TABLE 15. Residue Data from Citrus Processing Study with Propiconazole.

RAC Processed Commodity Total Rate

(lb a.i./250,000 lb fruit) 

DAA Propiconazole

Residues 

(ppm)

Processing 

Factor1

Orange Fruit (RAC) 0.40844 0 0.94 --

Juice <0.01 <0.01x

Dried pulp 1.29 1.4x

Oil 174 185x

1 Processing Factor = [Measured residue for analyte in the processed fraction] / [Measured residue for analyte in the RAC].

The observed processing factors for juice and oil are less than the theoretical concentration 

factors, based on separation into components, of 2x for juice and 1000x for oil (OPPTS 

860.1520, Table 3).

The citrus processing results acquired in this study are adequate for satisfying these data 

requirements. It produced sufficient data at the 1x application rate which is reflective of the 

proposed treatment program for evaluating the potential concentration of residues. These results 

indicate that propiconazole residues do not appear to concentrate in citrus juice, but do so in oil 

at a processing factor of 185x. Based on the HAFT residue for oranges (4.91 ppm) and the 

processing factor, expected residues are 908 ppm in citrus oil. A citrus oil tolerance of 1000 

ppm is therefore concluded to be appropriate with no limits being recommended for its other 

processed commodities. 

Meat, Milk, Poultry, and Eggs

Acceptable ruminant and poultry feeding studies were submitted and evaluated in conjunction 

with previous propiconazole petitions (PP#4F3074 and PP#1F3974). 

Field Accumulation in Rotational Crops

The nature of the residue in confined rotational crops is understood (D329394, Y. Donovan, 

6/15/06). Based on acceptable studies previously reviewed by EFED, the metabolism of 

propiconazole in rotational crops is similar to that in primary crops. Plant-back restrictions have 

been established for propiconazole products registered for use on rotational crops based on the 

confined rotational crop studies. Labels specify that any food/feed crops not listed on the label 

should not be planted within 105 days of treatment. Tolerances for inadvertent residues of 

propiconazole in/on alfalfa planted in rotation with propiconazole-treated crops have been 

established at 0.1 ppm for alfalfa forage and hay. 
Page 26 of 53

5.2 Dietary Exposure and Risk

Reference: Propiconazole: Acute and Chronic Aggregate Dietary (Food and Drinking Water) Exposure and Risk 

Assessments for the Snap Beans, Succulent Shelled Beans, Dry Beans, Citrus Fruit (post-harvest), Tomato (postharvest) and Stone Fruit (post-harvest).T. Morton, DP390248.drs, 1/26/12.

A new dietary assessment was conducted for the proposed Section 3 uses The proposed Section 3 uses 

on results dietary risk estimates below HED‘s level of concern; see Table 16.

Table 16. Summary of Dietary Exposure and Risk for Propiconazole FOOD PLUS 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 0.076469 25 0.021362 21

N/A

All Infants (< 1 year old) 0.087716 29 0.024867 25

Children 1-2 years old 0.231169 77 0.062701 63

Children 3-5 years old 0.166601 56 0.050566 51

Children 6-12 years old 0.107056 36 0.031980 32

Youth 13-19 years old 0.076315 25 0.020569 21

Adults 20-49 years old 0.058779 20 0.016313 16

Adults 50+ years old 0.048739 16 0.015572 16

Females 13-49 years old 0.062471 21 0.016676 17

Dietary Assessment of Free Triazole and its Conjugates

Reference: Common Triazole Metabolites: Updated Dietary (Food + Water) Exposure and Risk Assessment to 

Address The Amended Propiconazole Section 3 Registration to Add Uses on Snap beans, succulent shelled beans, 

dry beans, tomato (post-harvest, citrus (post-harvest), and stone fruit (post-harvest); The Amended Difenoconazole 

Section 3 Registration to Add Use on Root and Tuber group 1C; and the Amended Flutriafol Section 3 Registration 

to Add Use on Field Corn.T. Morton, DP397591.drs, 1/26/12.

The proposed Section 3 uses of propiconazole results in an increase in dietary exposure estimates for 

free triazole or conjugated triazoles. Therefore, the last dietary exposure analyses for the triazole 

metabolites needed to be updated. The proposed Section 3 uses on results dietary risk estimates below 

HED‘s level of concern; see Table 17.
Page 27 of 53

Table 17. Summary of Dietary (Food and Drinking Water) Exposure and Risk for the Common Triazole 

Metabolites Adding the new Section 3 Uses for Propiconazole, Flutriafol, and Difenoconazole.

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

1,2,4-Triazole

General U.S. Population 0.008892 30 0.001409 28

Not 

Applicable

Not 

Applicable

All Infants (< 1 year old) 0.012475 42 0.001923 39

Children 1-2 years old 0.023049 77 0.003723 75

Children 3-5 years old 0.017674 59 0.002994 60

Children 6-12 years old 0.011632 39 0.001891 38

Youth 13-19 years old 0.008196 27 0.001266 25

Adults 20-49 years old 0.006959 23 0.001162 23

Adults 50+ years old 0.006050 20 0.001097 22

Females 13-49 years old 0.007007 23 0.001166 23

Triazolylalanine + Triazolylacetic Acid 

General U.S. Population

Not 

Applicable

Not 

Applicable

0.019824 22

Not 

Applicable

Not 

Applicable

All Infants (< 1 year old) 0.020308 23

Children 1-2 years old 0.056263 63

Children 3-5 years old 0.045007 50

Children 6-12 years old 0.028078 31

Youth 13-19 years old 0.018635 21

Adults 20-49 years old 0.015881 18

Adults 50+ years old 0.014719 16

Females 13-49 years old 0.086155 86 0.016036 18

* The values for the highest exposed population for each type of risk assessment are bolded.

6.0 Residential (Non-Occupational) Exposure/Risk Characterization

No new residential uses are being requested at this time. Specifics concerning residential

handler exposure and risks are provided in the most recent occupational and residential exposure 

assessment for propiconazole (D349727, S. Oonnithan, 9/3/06).

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

This is particularly the case with aerial application (a method proposed to be employed for 

propiconazole), but, to a lesser extent, could also be a potential source of exposure from the 

ground application method also 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. On a chemical 

by chemical basis, 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 database 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 with specific products 

with significant risks associated with drift.
Page 28 of 53

7.0 Aggregate Risk Assessments and Risk Characterization

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

risks from three major sources: food, drinking water, and residential exposures (dermal and 

residential). 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.

7.1 Acute & Chronic Aggregate Risk

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

demonstrated under Section 5.2, acute and chronic aggregate risks are not of concern.

7.2 Short- and Intermediate-Term Aggregate Risk

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

levels to food and water (considered to be a background exposure level). Table 18 aggregates 

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

background). 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 short-term aggregate 

risk does not exceed HED‘s level of concern. This assessment is considered very conservative in 

that the residential incidental oral post-application exposure was calculated by combining three 

screening level assessments (which by themselves already have conservative estimates). 

Table 18: 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 N/A Oral 0.0627

30

480 2

130

Hand to Mouth Activity on Turf

100 1

Oral 0.0269 1100 3

Object to Mouth Activity on Turf Oral 0.0067 4500 3

Soil Ingestion Oral 0.00009 330,000 3

Turf –High-Contact Activities Dermal 0.1410 210 4

1 Target MOE= 100, Acute Neuortoxicity 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 19 aggregates the short-term risk for adults from residential handler exposure, and average 

food and water exposure (as a background). The lowest aggregate MOE is 110, which is greater 
Page 29 of 53

than the target MOE of 100. Adult handlers have some inhalation exposure, but there are no 

appropriate inhalation studies on propiconazole to assess their potential risk. Based on a recent 

effort to determine whether oral studies are predictive of inhalation toxicity, HED has concluded 

that the MOEs for inhalation exposure are sufficiently large that there is no concern for potential 

inhalation risk.

Table 19: Short-term Aggregate Risk Estimates to Propiconazole for Adults from Handler 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 0.0163 30 1800 2 NA

Ornamentals w Low Pressure 

Handwand

100 1

Dermal and 

Inhalation

0.0069

30

4400 31300

Ornamentals w Hose-end 

Sprayer 0.0008 40000 1700

Turf w Low Pressure 

Handwand 0.0237 1300 750

Turf w Hose-end Sprayer 0.0568 530 410

Applying Paint w Brush/ 

Roller 0.0323 330 280

Applying Paint w Airless 

Sprayer 0.2432 120 110

1 Target MOE= 100, Acute Neuortoxicity NOAEL=30

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

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

4 Aggregate Combined MOE (food, water, and residential) = 1÷ [(1÷MOE food and water) + (1÷MOE handler inhalation and

dermal)].

Table 20 aggregates the short-term risk for adults from residential post application, and average 

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

post application inhalation exposure is anticipated to occur. The highest post application 

exposure from residential use on turf was used in the short term aggregate. The aggregate MOE 

is 290, 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 30 of 53

Table 20: Short-term Aggregate Risk Estimates to Propiconazole for Adults from Post-Application 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 0.0163

30

1800 2

290 Residential Post-application 

(Residential Turf Gen. HighContact Activities))100 1 Dermal 0.085 350 3

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)].

7.2 Intermediate-Term Aggregate Risk 

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

propiconazole is post application exposure to children from wood treatment (antimicrobial use). 

Table 21 shows the aggregate risk for intermediate term exposure to Children 1-2 years old. The 

aggregate MOE is 74, which is less than the target MOE of 100. However, a refined chronic 

food and water exposure results in an MOE >100. Therefore, this scenario is not of concern.

Table 21. 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 N/A Oral 0.0627 10 160 2

Incidental oral 100 74 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)].

These aggregate exposure assessments are considered conservative estimates, that should not 

underestimate risks, for the following reasons: 1) the dietary inputs used tolerance-level residues, 

100% crop treated, and crop specific (turf) screening level drinking water modeling data (i.e., 

surface water modeling); 2) maximum application rates and minimum application intervals were 

used; and 3) conservative SOPs and upper level estimates of exposure were employed.
Page 31 of 53

Updated Aggregate Assessment of Free Triazole & its Conjugates

Reference: Common Triazole Metabolites: Updated Aggregate Human Health Risk Assessment to Address

Tolerance Petitions for Propiconazole, Difenoconazole, and Flutriafol. DP397592, T. Morton, 1/26/12.

The addition of the new proposed uses increase the aggregate exposure to free triazoles and its 

conjugates. Therefore, the aggregate human health risk assessment for free triazoles and its 

conjugates was updated and the aggregate estimates are below HED‘s level of concern

(DP397592, T. Morton, 1/26/12).

8.0 Cumulative Risk Characterization/Assessment

Propiconazole is a member of the triazole-containing class of pesticides. Although conazoles 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 conazoles, 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, the conazoles 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 conazoles share common mechanisms of toxicity 

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

for the conazoles. 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 is a triazole-derived pesticide. This class of compounds can form the common 

metabolite 1,2,4-triazole and two triazole conjugates (triazolylalanine and triazolylacetic 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, and triazolylacetic acid resulting from the use of all current and 

pending uses of any triazole-derived 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.
Page 32 of 53

9.0 Occupational Exposure/Risk Pathway

Reference: The occupational exposure and risk assessment was reviewed by the Exposure Science Advisory 

Council, the information provided in this Section comes from:. Propiconazole: Worker Risk Analysis for new uses 

on Beans (crop group 06), Tomatoes (crop group 08), Citrus (crop group 10), and Stone Fruit (crop group 12). 

DP390250, J. Miller, 1/19/12.

Occupational handler and post-application exposure scenarios were assessed for the proposed 

new uses. Based on the product labels and information provided by the registrant, short- and 

intermediate-term exposure is assessed for handlers and post-application activities. Dermal and 

inhalation exposures are aggregated for propiconazole because the toxicity endpoints for these 

exposure routes are not based on common toxicological endpoints. Labels for the propiconazole 

proposed uses require that applicators and other handlers wear personal protective equipment 

(PPE) consisting of long-sleeved shirt, long pants and shoes with socks plus gloves. 

9.1 Short- and Intermediate-Term Handler Risk

The term ―handler‖ applies to individuals who mix, load, and apply the pesticide product. 

There is a potential for exposure to propiconazole during mixing, loading, and application 

activities through the dermal and inhalation routes. Propiconazole products are applied using 

aerial, airblast, groundboom and chemigation equipment.

The quantitative exposure/risk assessment developed for occupational handlers is based on the 

following exposure scenarios: 

Mixer/Loaders

• Mixing/loading emulsifiable concentrates for aerial application

• Mixing/loading emulsifiable concentrates for groundboom application

Applicators

• Applying sprays aerially

• Applying sprays with groundboom sprayer

Flaggers

• Flagging for aerial spray application

Chemical-specific data for assessing exposure during pesticide handling activities were not 

submitted to the Agency in support of this Section 3 application. This risk assessment relies in 

part on data from studies in which adult human subjects were intentionally exposed to a pesticide 

or other chemical. These studies, which comprise the Pesticide Handlers Exposure Database 

(PHED), and the Agricultural Handler Exposure Task Force (AHETF), have been determined to 
Page 33 of 53

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

be ethical.

Summaries of the combined, dermal plus inhalation short-, and intermediate-term risks for each 

exposure scenario are presented in Table 18. The combined dermal and inhalation exposure 

risks are not of concern (i.e., MOEs >100), provided the mixer/loaders wear chemical-resistant 

gloves as directed on the label. 

An occupational and residential assessment was completed for similar use patterns (aerial, 

groundboom), which found that there were no risks of concern (J. Miller, 06/15/06, D325817). It

should be noted that in (D325817), the evaluated use pattern for the aerial, and groundboom 

exposure scenarios were more conservative for rice (i.e., 0.28 lb a.i./acre) for 1200 acres treated, 

than proposed in the current petition (i.e., 0.114 lb a.i./acre) for legume vegetables at 350 acres 

treated and therefore protective. Refer to; (J. Miller, 06/15/06, D325817) for toxicological 

endpoint data and previous calculation parameters. Margin of Exposure calculations were 

impacted due to a decrease in acres treated (legume vegetables vs. rice), application rate, and 

updated unit exposures1adopted by the Health Effects Division (HED). Exposure scenarios 

listed within (mixing/loading, applying, and flagging), risk estimates do not exceed HED‘s LOC 

(MOE < 100), and therefore not of concern to HED. See Table 22 for details.

 

1. 

1Note; HED policies on use of surrogate data, including their sources, are presented in the ―Occupational Pesticide Handler 

Unit Exposure Surrogate Reference Table‖ (http://www.epa.gov/pesticides/science/handler-exposure-table.pdf) and 

(http://www.epa.gov/pesticides/science/handler-exposure-data.html)
Page 34 of 53

Table 22: Occupational Short and Intermediate-Term Risk Assessment/Amended Uses of Propiconazole

Exposure 

Scenario Crops

Applicatio

n Rate

(lb a.i./A)1

Area 

Treated

(A/day)2

Dermal

Unit 

Exposure

(mg/lb a.i.)

3

Inhalation

Unit 

Exposure

( g/lb a.i.)

3

Dermal

Daily Dose

Inhalation

Daily Dose

ShortTermIntermediateTerm 

(mg/kg/day)4 MOE5

Combined dermal/inhalation

Mixer/Loader (emulsifiable concentrate)

6

Groundboom Legume

Vegetables 0.114

80

0.22 0.219

0.01147 0.0000285 2,600 870

Aerial 350 0.05016 0.0001248 600 200

Applying (emulsifiable concentrate)

Groundboom

(Open Cab) Legume

Vegetables 0.114

80 0.0786 0.34 0.004096 0.0000443 7,200 2,400

Aerial

(encl. Cockpit) 350 0.005 0.068 0.00114 0.0000388 25,000 8,500

Flagging (emulsifiable concentrate)

Aerial Flagging Legume

Vegetables 0.114 350 0.011 0.35 0.0025 0.0002 11,000 3,700

1. Application rates are based on maximum values found in proposed labels. 

2. Daily area treated is based on the area that can be reasonably applied in a single day for each exposure scenario. (Standard EPA/OPP/HED values).

3. HED policies on use of surrogate data, including their sources, are presented in the ―Occupational Pesticide Handler Unit Exposure Surrogate Reference Table‖ 

(http://www.epa.gov/pesticides/science/handler-exposure-table.pdf) and (http://www.epa.gov/pesticides/science/handler-exposure-data.html)

4. Daily Dose (mg/kg/day) was calculated by Unit Exposure * 40% absorption for dermal only * Appl. rate * Area treated} / 70 kg. 

5. Short-/Intermediate-Term MOE (dermal and inhalation endpoints are the same, therefore the MOEs are combined) = Dermal + Inhalation Dose 

/ NOAEL. Short-term NOAEL= 30 mg/kg/day and Intermediate-term NOAEL = 10 mg/kg/day. The LOC for the target MOE = 100.

Flagger 

The Agency has evaluated scenarios that may be limited in nature such as flagging during aerial 

applications because engineering controls (i.e. Global Positioning Satellite technology) are now 

predominantly used as indicated by the 1998 National Agricultural Aviation Association 

(NAAA) survey of their membership. It appears, however flaggers are still used in 

approximately 10 to 15 percent of aerial application operations. In cases like these, the Agency 

strongly encourages the use of the engineering control system, but will continue to evaluate risks 

for flaggers and any other population where a clear exposure pathway exists until the potential 

for exposure is eliminated. The Agency is aware that NAAA is conducting another survey of its 

membership on exposure issues and will consider those results as is timely and appropriate.

For pesticide handlers, HED presents estimates of dermal exposure for ―baseline‖ (i.e. workers 

wearing a single layer of work clothing consisting of a long sleeved shirt, long pants, shoes, plus 

socks and no protective gloves, as well as for ―baseline‖ and the use of protective gloves or other 

personal protective equipment (PPE), as might be necessary. The propiconazole product labels 

for foliar treatments recommend applicators and other handlers to wear long-sleeved shirt and 

long pants, and shoes plus socks. 
Page 35 of 53

Handler Exposure - Post Harvest Use Pattern

According to label; [(Tilt® 45W (EPA Reg. No.:100-780)], propiconazole can be applied to 

tomatoes, citrus, and stone fruit after harvest inside packing facilities using a T-jet or CDA 

system. Application methods, maximum application rates, and use sites are summarized in Table 

1. Handler exposure is expected to be short- or intermediate-term based on information provided 

on the proposed label. 

Exposure Scenarios

The quantitative occupational exposure/risk assessment for the use of propiconazole on postharvest crops is based on the mixing and loading of wettable powders only. 

Open Mixing and Loading of wettable powders

Application of propiconazole solutions are typically automated with commodities passing 

through sprays/foams/brushes on conveyor belts or bins being mechanically dipped. The 

commodities are then manually sorted and packed by workers at the end of the process. 

Note: Application of solutions by dipping, drenching, brushing, spraying are not typical 

―applicator‖ scenarios. The assessment for automated application estimates exposures and 

risks for workers in the vicinity of the application process; therefore exposure during the 

application of a post-harvest pesticide is expected to be limited to mixing and loading. See 

(D. Jaquith, 11/2005) for details.

Personal Protective Equipment

Baseline PPE: includes typical work clothing (i.e., a long-sleeved shirt, long pants, 

shoes, socks, and no respiratory protection). It does not include chemical-resistant 

gloves.

Baseline/Gloves PPE: includes chemical-resistant gloves in addition to baseline PPE. 

Note: most labels call for handlers to don at least this level of protection

Data and Assumptions for Post Harvest Handler Exposure Scenarios

An Expo-SAC draft policy (D. Jaquith, 11/2005) is used to assess exposure from post-harvest 

application to tomatoes, citrus, and stone fruit. The draft SOP indicates that procedures (and 

therefore exposure estimates) are essentially the same for all post-harvest products. The draft 

SOP outlines exposure estimates from application to harvested citrus because it is assumed that 

citrus facilities have the highest throughput compared to facilities treating other commodities. 

However, some label-specific information was used in this assessment. 
Page 36 of 53

The estimates of exposure and risk resulting from these calculations should be considered 

conservative for the following reasons: 1) workers are not assumed to wear any protective 

clothing while mixing/loading the material for post-harvest treatments; 2) the material is not 

assumed to be recycled, while in practice some chemical solutions are recycled/re-used 3 to 5 

times before new formulation is mixed; and 3) when generic citrus estimates were used, other 

commodities may not have the throughput associated with a large citrus packing plant. Using the 

generic estimates in the draft SOP and label-specific information, the exposure assessment was 

calculated using the following data and assumptions: 

Unit Exposures

No chemical-specific handler exposure data were submitted in support of this 

registration. To assess handler exposures for regulatory actions when chemical-specific 

monitoring data are not available, HED relies on the most scientifically-reliable surrogate 

data currently available from various sources such as the Pesticide Handlers Exposure 

Database (PHED), and the Agricultural Handler Exposure Task Force (AHETF). Some of 

this data, such as the industry task force data, is compensatory, subject to the data protection 

provisions of FIFRA. HED policies on use of surrogate data, including their sources, are 

presented in the ―Occupational Pesticide Handler Unit Exposure Surrogate Reference Table‖ 

(http://www.epa.gov/pesticides/science/handler-exposure-table.pdf) and 

(http://www.epa.gov/pesticides/science/handler-exposure-data.html). 

Max Application Rates

The label-specified amount of propiconazole to treat post-harvest tomatoes was (8 oz. per 

50,000 lbs. of tomatoes).

The label-specified amount of propiconazole to treat post-harvest citrus was (16 oz. per 

250,000 lbs.) of citrus.

The label-specified amount of propiconazole to treat post-harvest stone fruit was (4 oz.

per 250,000 lbs.) of stone fruit.

Amount Treated/Processed 

Based on the draft SOP (D. Jaquith, 11/2005), which uses citrus packing as the 

most conservative post-harvest scenario, HED assumes that a facility can process up to 2,000 

boxes per hour, each weighing 90 pounds. This throughput is protective for tomatoes and 

stone fruit.

Body Weight

The average adult body weight of 70 kg., was used for calculations.
Page 37 of 53

Absorption Factors

The short- and intermediate-term dermal absorption factor is 40%. 

 Equations and Calculations

Maximum Application Rate: The maximum application rate was calculated by using the 

proposed lbs. a.i. of product per lbs. of specific crop. 

Max. App. Rate (lbs a.i./lbs specific crop.) = oz. product/lbs. specific crop x 1 lb/16 oz. x 45% a.i. 

Amount Treated/Processed per Day: The amount treated per day was calculated by using 

the proposed default values per day. 

o Amount Processed: Default citrus value of 2,000 boxes per hour, each weighing 

90 lbs. An 8-hr workday is assumed

 

Amount processed (lbs crop/day) = 2,000 boxes/hr x 90 lbs x 8 hrs/day

For post harvest in-line dip/drench and or a coating spray exposure scenario to Tomatoes (crop 

group 08), Citrus (crop group 10), and Stone Fruit (crop group 12), risk estimates do not exceed 

HED‘s LOC (MOE < 100), and therefore not of concern to HED. See Table 23 for details.
Page 38 of 53

9.2 Short- and Intermediate-Term Post-Application Risk

Agricultural workers performing typical post-application activities may receive exposure to 

propiconazole residues. 

Occupational Post-application Exposure and Risk

HED uses the term post-application to describe exposures that occur when individuals are 

present in an environment that has been previously treated with a pesticide (also referred to as a 

re-entry exposure). Such exposure may occur when workers enter previously treated areas to 

perform job functions, including activities related to crop production, such as scouting for pest or 

harvesting. In the case for propiconazole, post-application dermal exposure to field workers 

following foliar applications is probable, whereas propiconazole is a fungicide that can be 

applied to all stages of growth. Since no post-application data were submitted in support of the 

registration action, dermal exposures during post-application activities were estimated using 

dermal transfer coefficients from the Science Advisory Council for Exposure Policy Number 3 

(http://www.epa.gov/pesticides/science/exposac_policy3.pdf), and summarized in Table 20

below. 

Table 23. Occupational Handler Short- and Intermediate-Term Dermal and Inhalation Exposure and Risk Estimates for 

Tomato, Citrus, and Stone Fruit Post-Harvest Use 

Activity/

Exposure 

Scenario 

Max App. 

Rate1

(lb a.i./lbs. 

crop)

Amount 

Treated/

Processed 

Crop Specific2

(lbs. crop/day)

Inhalation 

Unit Exp.3

(mg/lb a.i.)

Dermal Unit 

Exp.3

(mg/lb a.i.)

ST & IT 

Inhalation 

Daily Dose4 

(mg 

a.i./kg/day)

ST & IT Dermal 

Daily Dose4 

(mg a.i./kg/day)

ShortTerm 

MOE5

Inter. -

Term 

MOE5

Baseline W/ 

gloves Baseline W/ gloves

Dermal + 

Inhalation

Baseline8

With

Gloves

Tomato (Crop Group 8) Wettable Powders2

Open Mixing/

Loading 0.225/50,000 1,440,000 0.0434 3.7 .17 0.00402 0.137 0.0063 210 71 970

Citrus (Crop Group 10) Wettable Powders

Open Mixing/

Loading 0.450/250,000 1,440,000 0.0434 3.7 0.00161 0.0548 530 62,000

Stone Fruit (Crop Group 12) Wettable Powders

Open Mixing/

Loading 0.113/250,000 1,440,000 0.0434 3.7 0.00040 0.014 75,000 25,000

1. Max appl. Rate on label : [(oz. product/lbs. crop) x (lb/16 oz.) x (45% a.i.) = (lb a.i. / lbs. crop)]. Wettable Powder Formulation - Tilt® 45W (EPA Reg 

No.: 100-780) 45%.

2. Amount Treated/Processed Per day (lbs. crop/day) = 2000 boxes/hr x 90 lbs/box x 8 hrs/day 

3. Unit Exposure Values -Baseline PPE: includes typical work clothing (i.e., a long-sleeved shirt, long pants, shoes, socks, and no respiratory protection). 

It does not include chemical-resistant gloves....except for the tomato scenario, where gloves were added to achieve an MOE > 100

4. Daily Dose - [Max. App Rate (lbs a.i./lbs. crop) x Amount Treated/Processed (lb crop/day) x Unit Exposure (mg/lb a.i.) x absorption factor (.40, applicable 

to dermal route only)]/ 70-kg body weight

5. Short/Intermediate- Term MOE (dermal and inhalation endpoints are the same, therefore the MOEs are combined) = Dermal + Inhalation Dose / NOAEL. 

Short-term NOAEL= 30 mg/kg/day and Intermediate-term NOAEL = 10 mg/kg/day. The LOC for the target MOE = 100
Page 39 of 53

The following assumptions were used for all calculations:

Body Weight

The average adult body weight of 70 kg was used for calculations.

Absorption Factors

The short- and intermediate-term dermal absorption factor is 40%. 

Application Rate

Application rate = 0.114 lbs a.i./Acre

Exposure Duration

8 hours/Day

The fraction of a.i. retained on foliage is assumed to be 20% (0.2) on the day of application (= % 

dislodgeable foliar residue, DFR, after initial treatment) for agricultural crops. This fraction is 

assumed to further dissipate at the rate of 10% (0.1) per day on following days. These default 

values have been established by HED ̳s Science Advisory Council (SAC) for Exposure. 

Note: For specifics concerning all post-application studies as they refer to propiconazole-specific 

dissipation data, (see Memorandum, DP #: 329393 titled, Propiconazole: Phase IV revised 

Occupational and Residential Exposure Assessment for the Re-registration Eligibility Decision 

Document (RED) for details. 

Post-application MOEs were estimated for ―Day 0" exposure (i.e., the day of application). As 

shown in Table 24, the short-/intermediate-term MOEs are greater than 100 on the day of 

application for all agricultural crops. 
Page 40 of 53

Post-application Exposure Calculations:

Daily Exposure: The next step in the risk assessment process was to calculate dermal exposures 

on each day after application using the following equation. 

o DFRt = AR x F x (1-D)tx CF1 x CF2

Where:

DFRt = dislodgeable foliage residue on day ―t‖ (μg/cm2)

AR = application Rate (lb ai/acre)

F = fraction of a.i. retained on foliage (unitless)

D = fraction of residue that dissipates daily (unitless)

CF1 = conversion factor, 4.54E+8μg/lb

CF2 = conversion factor, 2.47E-8acre/cm2

Daily Dermal Dose and Margins of Exposure: Once daily exposures are calculated, the 

calculation of daily absorbed dose and the resulting Margin of Exposures use the equations 

shown below. These calculations are completed for each day or appropriate block of time after 

application.

o Daily Dermal Dose = DFRt x CF1 x TC x DA x ET) / BW

Where:

Daily Dermal dose = Absorbed dose received from exposure to a pesticide in a

 given scenario on day ―t‖ (mg/kg/day)

DFRt = Dislodgeable foliage residue on day ―t‖ (μg/cm2)

CF1 = Conversion factor, 1E – 3 mg/μg

TC = Transfer coefficient (cm2/hr)

DA = dermal absorption factor (unitless)

ET = exposure time (hr/Day)

BW = body weight (kg)

o MOE = POD (mg/kg/day) / Daily Dermal Dose (mg/kg/day)

 

Post-application Exposure Summary: Legume Vegetables

Risk estimates do not exceed HED‘s LOC (MOE < 100), and therefore not of concern to HED. 

See Table 24 for details.
Page 41 of 53

1 Maximum application rate from proposed label 

 2 DAT = Days after treatment needed to reach the LOC of 100; DAT 0 = the day of treatment/ assumed to be approx. 12 hours. 

 3 DFR (μg/cm2

) = dislodgeable foliar residues corresponding to DAT, based on 20% of application rate.

 4 TC (cm2

/hr) = transfer coefficients and associated activities from Expo-SAC Policy Memo #003.1, 8/17/2000.

5 MOE = MOE on the corresponding DAT. MOE = NOAEL / Daily Dose. 

 Short-Term NOAEL = 30 mg/kg/day. 

 Intermediate-term NOAEL = 10 mg/kg/day. 

 The LOC is 100. 

* Daily Dose = [(DFR x TC x 40% Dermal absorption x 8-hr Exposure Time)] / [(CF: 1000 μg/mg) x (70-kg Body Weight) 

Post Harvest - Post-application Exposure and Risk

Propiconazole is applied as a post harvest treatment to citrus, stone fruit and tomatoes either as a 

coating spray or during in-line dip procedures. Post application exposure may occur during 

sorting/packing/culling operations. The estimates of post application exposure can be derived 

from residue chemistry data, surface area calculations, and a reentry study for citrus found in the 

scientific literature, and a study monitoring the amount of material transferred during contact 

with a treated surface. See an Expo-SAC draft policy (D. Jaquith, 11/2005), for details.

Data and Assumptions for Post Harvest Handler Exposure Scenarios

The residue level of propiconazole in oranges from post-harvest field trials is 4.91 ppm 

(μg/g); (see MRID No. 48438205). 

Pesticide residue is on the surface of the commodity. The chemical is not applied as a 

systemic product. 

Workers are assumed to perform the sorting/culling tasks for 8 hours per day.

Dermal absorption is 40%.

The transfer efficiency of the chemical is less than 2%. 

The transfer coefficient for the palmar surface of the hands only = 408 cm2 per hour.

Table 24. Summary of Estimated Post-application MOEs for Legume Vegetables

Crop

Application 

Rate

(lb a.i./A) 1

DAT2 DFR 3

(μg/cm2)

TC 4

(cm2/hr) Activity 4

ShortTerm 

InterTerm

MOE5

Legume Vegetables

(Crop Group 06) 0.114 0 0.256

70 Hand weeding, Thinning 37,000 12,000

210 Scouting 12,000 4,100

1,100 Scouting 2,300 780

1,900 Irrigation (hand set) 1,400 450
Page 42 of 53

Post Harvest: Post-application Exposure Calculations:

Propiconazole residue on the surface of the Navel orange can be calculated as follows:

Propiconazole (μg/orange) = 4.91 μg/g x 165 g/orange = 810.15 μg/orange

The surface area of a ―Navel‖ orange is:

Surface Area = 167.42 cm2

The pesticide residue assumed to be on the surface and available for transfer would therefore be:

810.15 μg/167.42 cm2 = 4.84 μg/cm2

With a transfer coefficient of 408 cm2/hr and a transfer efficiency of 2%, the dermal dose of a 70 

kg individual becomes:

Dermal dose calculation:

(408 cm2/hr) x (4.84 μg/cm2) x (8 hrs/day) x 0.4 x 0.02 x 0.001 mg/μg

 70 kg

= 0.00181 mg/kg/day

Post Harvest: Post-application Exposure Summary: 

Risk estimates do not exceed HED‘s LOC (MOE < 100), and therefore not of concern to HED. 

See Table 25 for details.
Page 43 of 53

Table 25. Summary of Estimated Post Harvest Post-application MOEs for Citrus.

Commodity

Chemical in Specific 

Commodity Chemical Specific

Commodity 

Specific 

Surface area

Surface 

Residue Dermal Dose ShortTerm 

MOE2

IntTerm 

MOE2

1

μg /g g /Commodity μg / Commodity (cm2) (μg/cm2) (mg /kg / day)

Citrus

(Navel Orange)3 4.91 165 810.15 167.42 4.84 0.00181 16,600 5,500

1Residue level calculations for Navel Orange: (MRID No. 48438205)

2 MOE = MOE = NOAEL / Daily Dose. Short-Term NOAEL = 30 mg/kg/day. Intermediate-term NOAEL = 10 mg/kg/day. The LOC is 100 

*Daily Dose = [(Surface Residue x TC (408 cm2/hr) x 40% Dermal absorption x 2% transfer efficiency x 8-hr Exposure Time)] / [(CF: 1000 

μg/mg) x (70-kg Body Weight)].

3Citrus: (Navel Orange) used in calculations because it has the highest residue from citrus crop field trials (MRID, and protective 

of other (Crop Group 10) commodities.

Post-Application Inhalation: Based on the Agency's current practices, a quantitative 

occupational post-application inhalation exposure assessment was not performed for 

propiconazole at this time; an inhalation exposure assessment was performed for occupational 

handlers. This assessment resulted in risk estimates that did not exceed HED’s level of 

concern at baseline inhalation PPE. Handler exposure resulting from application of pesticides 

outdoors is likely to result in higher exposure than post-application exposure. Therefore, it is 

expected that these handler inhalation exposure estimates would be protective of most 

occupational post-application inhalation exposure scenarios. However, there are multiple 

potential sources of post-application inhalation exposure to individuals performing postapplication activities in previously treated fields. These potential sources include volatilization 

of pesticides and re-suspension of dusts and/or particulates that contain pesticides. The Agency 

sought expert advice and input on issues related to volatilization of pesticides from its Federal 

Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009. 

The Agency received the SAP‘s final report on March 2, 2010 

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

process of evaluating the SAP report as well as available post-application inhalation exposure 

data generated by the Agricultural Reentry Task Force and may, as appropriate, develop policies 

and procedures, to identify the need for and, subsequently, the way to incorporate occupational 

post-application inhalation exposure into the Agency's risk assessments. If new policies or 

procedures are put into place, the Agency may revisit the need for a quantitative occupational 

post-application inhalation exposure assessment for propiconazole. 
Page 44 of 53

Appendix A: Toxicology Assessment

A.1 Toxicology Data Requirements

Table A.1. Propiconazole Toxicology Data Requirements

Guideline Data Requirements

Test Technical

Required Satisfied

870.1100 Acute Oral Toxicity.......................................................

870.1200 Acute Dermal Toxicity ..................................................

870.1300 Acute Inhalation Toxicity..............................................

870.2400 Primary Eye Irritation....................................................

870.2500 Primary Dermal Irritation ..............................................

870.2600 Dermal Sensitization......................................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.3100 Oral Subchronic (rodent)...............................................

870.3150 Oral Subchronic (nonrodent) .........................................

870.3200 21-Day Dermal ..............................................................

870.3250 90-Day Dermal ..............................................................

870.3465 90-Day Inhalation..........................................................

yes

yes

yes

no

yes

yes

yes

yes

-

yes

870.3700a Developmental Toxicity (rodent)...................................

870.3700b Developmental Toxicity (nonrodent).............................

870.3800 Reproduction .................................................................

yes

yes

yes

yes

yes

yes

870.4100a Chronic Toxicity (rodent) ..............................................

870.4100b Chronic Toxicity (nonrodent)........................................

870.4200a Oncogenicity (rat)..........................................................

870.4200b Oncogenicity (mouse)....................................................

870.4300 Chronic/Oncogenicity....................................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.5100 Mutagenicity—Gene Mutation - bacterial.....................

870.5300 Mutagenicity—Gene Mutation - mammalian................

870.5375 Mutagenicity—Structural Chromosomal Aberrations...

870.5900 Mutagenicity—Other Genotoxic Effects.......................

yes

yes

yes

yes

yes

yes

yes

yes

870.6100a Acute Delayed Neurotox. (hen) .....................................

870.6100b 90-Day Neurotoxicity (hen)...........................................

870.6200a Acute Neurotox. Screening Battery (rat) .......................

870.6200b 90-Day Neuro. Screening Battery (rat)..........................

870.6300 Develop. Neuro..............................................................

no

no

yes

yes

no

-

-

yes

no

-

870.7485 General Metabolism ......................................................

870.7600 Dermal Penetration ........................................................

870.7800 Immunotoxicity .............................................................

yes

no

yes

yes

-

no
Page 45 of 53

A.2 Toxicity Profiles

Table A.2: Propiconazole Acute Toxicity Profile

GuidelineNo. Study Type MRID # Results Toxicity Category

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

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

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

870.2400 Acute Eye Irritation 00058597 Corneal opacity reversed in 72 hrs III

870.2500 Acute Dermal Irritation 00058598 No irritation IV

870.2600 Skin Sensitization 44949501 confirmed sensitizer -

Table A.3 Subchronic, Chronic and Other Toxicity Profile: Propiconazole

Guideline No./ Study 

Type

MRID No. (year)/ 

Classification /Doses

Results

870.3100

90-Day Feeding 

Study in Rat

00058606 (1997)

Acceptable/Guideline

0, 240, 1200 or 6000 ppm

(M: 0, 15.9, 76.1, 461.7, F: 

0, 16.8, 77.6, 400.9 

mg/kg/day )

LOAEL = 6000 ppm in males (462 mg/kg bw /day) and 1200 ppm 

in females (77.59 mg/kg bw/day) based on reduced body weight 

gain. 

NOAEL = 1200 ppm in males (76 mg/kg bw/day) and 240 ppm in 

females (16.82 mg/kg bw/day).

870.3100

3-month oral toxicity 

study - mice

42050501,(1991)

Acceptable/Guideline

0, 20 500 or 2500 ppm 

(M: 0, 2.7, 65, or 352, 

F: 0, 3.4, 85, 434 

mg/kg/day) Two additional 

male groups at 850, 1450 

ppm (112, 194 mg/kg/day)

LOAEL = 500 ppm (65 mg/kg/day) in males and 2500 ppm (434 

mg/kg/day) in females based on increase in absolute and relative 

liver weights and histopathological changes (hypertrophy, necrosis).

NOAEL is 20 ppm in males (2.7 mg/kg/day) and 500 ppm in 

females (85 mg/kg/day).

870.3100

3-month oral - male 

mice 

42050502 (1991)

Acceptable/Guideline

0, 20, 500, 850, 1450 ,2500 

ppm

(0, 2.7, 65, 112, 194, 352 

mg/kg/day

LOAEL = 500 ppm (65 mg/kg/day), based on increase in absolute 

and relative liver weights and histopathological liver lesions 

(hypertrophy, necrosis, vacuolation) seen at 4, 8 and 13 weeks 

sacrifices. The NOAEL is 20 ppm (2.7 mg/kg/day)

870.3100

3-month oral - male 

mice. 

45215801 (1997) 

Supplement to MRID 

42050502: Reexamination 

of liver

Confirms findings in MRID 42050502. No change to NOAEL or 

LOAEL

870.3150

3-month dog (dietary)

00058607(1979) 

Acceptable/Guideline

0, 50, 250 or 1250 ppm

(0, 1.25, 6.25, 31.25 

mg/kg/day)

LOAEL is 250 ppm (59 mg/kg/day) based on the finding of 

lymphoid follicles in the mucous membrane of the pyloric part of 

the stomach. 

NOAEL is 50 ppm (13mg/kg/day) 
Page 46 of 53

Table A.3 Subchronic, Chronic and Other Toxicity Profile: Propiconazole

Guideline No./ Study 

Type

MRID No. (year)/ 

Classification /Doses

Results

870.3200

21 - Day dermal 

toxicity - rabbits

00116591 (1982)

Acceptable/Guideline

0, 3, 30 or 300 mg/kg/day

LOAEL: 3 mg/kg/day based on mild dermal irritation 

(Hyperkeratosis, acanthosis, mild dilation of blood vessels and 

mononuclear cells and/or heterophils in the proximal dermis). No 

systemic toxicity was reported.

NOAEL for skin lesions not established

870.3700a

Developmental 

Toxicity- Rat

40425001(1987)

Acceptable/guideline

0, 30, 90 or 300 mg/kg/day

Maternal Toxicity LOAEL = 300 mg/kg/day based on severe 

clinical toxicity (ataxia, coma, lethargy, prostation, labored 

respiration and salivation)

NOAEL = 90 mg/kg/day

Developmental Toxicity LOAEL = 90 mg/kg/day based on 

increased incidence of rudimentary ribs, cleft palate malformations 

(0.3%) unossified sternebrae, as well as increased incidence of 

shortened and absent renal papillae.

NOAEL = 30 mg/kg/day

Non-guideline

Developmental 

Toxicity- Rat

40425002 (1987)

Acceptable/non-guideline

0 or 300 mg/kg/day

cleft palate: 2/2064 fetuses of dosed animals vs. 0/1222 controls 

(lab.hist. control incidence: was 0/5431). This confirms findings of 

cleft palate noted in above study.

Severe clinical toxicity in the treated animals (ataxia, coma, 

lethargy, prostation, labored respiration and salivation)

870.3700b

Developmental 

Toxicity- Rabbit

40425004 (1986)

Acceptable/guideline

0, 100, 250 or 400 

mg/kg/day

Maternal Toxicity LOAEL = 250 mg/kg/day based on reduced dam 

body weight gain and decreased food consumption during the 

dosing period

NOAEL = 100 mg/kg/day

Developmental Toxicity 

LOAEL = 400 mg/kg/day based on increased incidence of fetuses 

/litters with 13thrib and increased abortions.

NOAEL = 250 mg/kg/day

870.3800

2-Generation 

reproduction- Rat

00151514 (1985)

Acceptable/guideline

0, 100. 500 or 2500 ppm

Parental Toxicity LOAEL = 500 ppm (42 mg/kg/day) based on 

increased incidence of hepatic clear cell change

NOAEL = 8 mg/kg/day

Reproductive Toxicity

LOAEL =>2500 ppm (>263 mg/kg/day, HDT)

Offspring Toxicity 

LOAEL = 2500 ppm (192-263 mg/kg/day based on decreased 

offspring survival and body weights and an increased incidence of 

hepatic cellular swelling

NOAEL = 500 ppm (43-52 mg/kg/day)

870.4100

12-Month Chronic 

Oral Toxicity 

(dietary) - Dogs

00151515 (1985)

Acceptable/guideline

0, 5, 50 or 250 ppm

(0, 0.12, 1.25, or 6.25 

mg/kg/day)

LOAEL = 250 ppm (6.25 mg/kg/day), based on hyperemia of the 

stomach in males (indicating mild irritation of the mucosa).

NOAEL is 50 ppm (1.25 mg/kg/day)
Page 47 of 53

Table A.3 Subchronic, Chronic and Other Toxicity Profile: Propiconazole

Guideline No./ Study 

Type

MRID No. (year)/ 

Classification /Doses

Results

870.4100

24-Month 

Chronic/Carcinogenic

ity Feeding-Rats

00129918 (1982)

Acceptable/guideline

0, 100, 500 or 2500 ppm

(male 3.6, 18.1 and 96.4 , 

female 4.6, 23.3 and 100.6 

mg/kg/day)

LOAEL = 2500 ppm (96.4 mg/kg/day) based on liver lesions 

(vacuolation of hepatocytes in males, ballooned cells in the liver of 

males, foci of enlarged hepatocytes in females, and increased 

incidence of luminal dilation of the uterus) and reduced body 

weight gain in both males and females. NOAEL = 500 ppm (18.1 

mg/kg/day). The test material was not carcinogenic at the doses 

tested. 

870.4200

24-Month 

Carcinogenicity in 

Mice

00129570 (1982 )

Acceptable/guideline

0, 100, 500 or 2500 ppm

(M: 10.0, 49.4, and 344.3 

F: 10.8, 55.6 and 340.3 

mg/kg/day

LOAEL = 500 ppm (49.5 mg/kg/day) based on non-neoplastic liver 

effects (increased liver weight in males and increase in liver lesions 

(masses/raised areas/ swellings/nodular areas mainly)). The 

NOAEL was 100 ppm (10 mg/kg/day).

Liver tumors at 2500 ppm in male mice.

870.4200

18 - month 

oncogenicity study -

male CD-1 mice

44381401 (1997)

Acceptable/guideline

0, 100, 500 or 850 ppm

(0, 11, 59 or 108 

mg/kg/day)

LOAEL= 500 ppm (59.0 mg/kg/day) for males, based on 

hepatotoxicity (increased liver weight, hepatocellular hypertrophy, 

liver necrosis) and body weight gain effects observed at the interim 

and terminal sacrifices. 

NOAEL= 100 ppm (11.0 mg/kg/day) for males.

Treatment related increase in hepatocellular adenoma and total 

hepatocellular neoplasia at the 850 ppm exposure level compared to 

concurrent controls, but were within the range of the inadequate 

historical control data submitted with the study report. Adequate 

dosing based on body weight gain and hepatotoxic effects seen at 

500 and 850 ppm. Subsequently, the Registrant submitted 

additional control data on five groups of CD-1 male mice generated 

within the approximate time frame of the original study and in the 

same testing facility under similar experimental conditions (MRID 

45215804) concerning the spontaneous occurrence of liver tumors. 

The tumor incidence observed in male livers at the 850 ppm dose is 

within the range of the new historical data. 

870.6200 

Acute neurotoxicity 

in rats

46604601 (2005)

Acceptable/guideline

0, 30, 100 or 300 mg/kg by 

gavage

LOAEL = 100 mg/kg based on clinical signs of toxicity 

(piloerection, diarrhea, tiptoe gait). 

NOAEL = 30 mg/kg.

LOAEL for neurobehavioral toxicity = 300 mg/kg based on reduced 

motor activity.

NOAEL for neurobehavioral toxicity = 100 mg/kg

870-5100

Bacterial reverse 

mutation

00058601 (1979)

Unacceptable

25-2025 g/plate

Negative in Salmonella strains with or without S-9 activation. Test 

material purity not specified, not tested up to cytotoxic dose.
Page 48 of 53

Table A.3 Subchronic, Chronic and Other Toxicity Profile: Propiconazole

Guideline No./ Study 

Type

MRID No. (year)/ 

Classification /Doses

Results

870-5300

In vitro cell 

transformation assay 

(BALB/3T3)

00133349 (1982)

Acceptable/guideline

1.16-18.5 g/ml

Did not cause a measurable increase in transformation of BALB/T3 

cells. Highest dose produced 25% reduction in colony forming 

ability.

870-5385

(bone marrow 

chromosomal 

aberration) - Chinese 

hamsters 

00058603 (1979)

Acceptable/guideline

0, 251, 502 or 1004 mg/kg

Negative for induction of micronuclei in bone marrow cells at all 

levels tested.

870-5550

Unscheduled DNA 

synthesis in human 

fibroblasts,

00133347 (1982)

Acceptable/guideline

Negative for inducing Unscheduled DNA Synthesis at 

concentrations up to and including 9.32 μg/ml. Highest dose tested 

to allow at least 25% cell viability

870-5550

Unscheduled DNA 

synthesis in primary 

rat hepatocytes

00133348 (1982)

Acceptable/guideline

Negative for inducing Unscheduled DNA Synthesis at 

concentrations up to and including 83.5μg/ml. Highest dose tested 

to allow at least 25% cell viability

870-5575

Mitotic gene 

conversion assay 

(Saccharomyces 

cerevisiae)

00133343 (1982)

Acceptable/guideline 

10, 30, 90 or 270 g/ml

No increase in convertants or revertants (did not induce mutation) 

with or without activation. Concentrations of 30 g/ml had 

inhibitory effect on yeast cell growth.

870.5450

Dominant lethal assay 

in mice

00058602 (1979)

Acceptable/guideline 

165 or 495 mg/kg single 

dose oral gavage, 

No evidence of dominant lethal effects was observed in the progeny 

of mice treated with propiconazole.

870.7485

Metabolism and 

pharmacokinetics

(Rat)

42403901 (1983)

Acceptable/guideline

male rats: single oral 

31.4 mg/kg -

14C at the 

triazole-[3,5] position

Rapidly metabolized: 96% excreted in urine and feces (5:4 ratio) 

after 3 days. Extensively metabolized by hydroxylation, oxidation 

and conjugation.

870.7485

Metabolism and 

pharmacokinetics

(Rat)

41326701 (1989)

Acceptable/guideline

0.5 mg/kg oral or iv (U14C)-Phenyl label or 0.5 

mg/kg/day unlabeled for 

14 days followed with 0.5 

mg/kg labeled or single 

oral dose 50 mg/kg labeled

Oral or iv routes resulted in similar patterns of 14C elimination 

suggesting biliary excretion. >90% of 14C excreted after 168 hours 

mostly within the 48 hrs. Females eliminated more in the urine 

than in the feces and vice versa for males in the orally dosed 

groups. No significant differences were seen in the excretion pattern 

or were seen between the low and high dose groups or the repeated 

dosing groups. Extensively metabolized (oxidative): 24 and 47 

metabolites in urine and feces, respectively. Parent (27-30% of 

AD) only detected in the urine of iv animals.
Page 49 of 53

Table A.3 Subchronic, Chronic and Other Toxicity Profile: Propiconazole

Guideline No./ Study 

Type

MRID No. (year)/ 

Classification /Doses

Results

870.7485

Metabolism and 

pharmacokinetics

(Rat)

00074506 (1979)

00074507 (1981)

Acceptable/guideline

triazole-[3,5-

14C] labeled 

single oral dose of 31.4 

mg/kg or phenyl-[U14C] 

single oral dose of 32.5 

mg/kg to male rats. 

Study focused on urinary and fecal metabolites. Similar metabolic 

profiles for the two labels suggesting that the bridge between the 

phenyl ring and the triazole ring remained intact. Metabolic 

pathway: cleavage of dioxolane ring through the oxidation of the 

propyl side chain, with subsequent dechlorination and conjugation 

and through the oxidation of the propyl side chain. Urinary and 

fecal metabolites except the presence of parent in feces.

870.7485

Metabolism and 

pharmacokinetics 

(Mouse)

00164795 (1986)

Acceptable/non-guideline

Male and female mice fed 

in the diet for 21 days at 5, 

100 or 2500 ppm 

propiconazole followed by 

phenyl-[U14C] single oral 

dose at corresponding 

levels. Two male rats 

given single oral dose 9.4 

mg/kg of the phenyl-[U14C]compound

Mice pre-treated with the unlabeled CGA 64250 excreted 83-103% 

of the administered 14C radioactivity within 96 hours (mostly within 

the first 24-48 hours) in the urine and feces (mostly in urine: 1.5-

3.7x of the feces). The male rats excreted nearly equal amounts of 

the radioactivity in urine (48%) and feces (54%). Mouse urinary 

metabolites 15-30. The major metabolic pathway in mice proceeds 

via elimination of the dioxolane ring. In males this represents 30% 

of the AD whereas in the females it represents 15% of the AD. 

Mice cleaved the dioxolane ring to a greater extent (70% & and 

40% for males and females, respectively) than do male rats (30%). 

870.7600

Dermal penetration

(Rat)

42415701 (1986)

Acceptable/guideline

Propiconazole 14C at the 

triazole-[3,5] position

0.01, 0.1, 1.0 mg/cm2

The average dermal absorption of propiconazole over a 10 hour 

period at an exposure level of 0.01 mg/cm2is approximately 40%

Non- guideline

Special study 

00151517 (1984)

Acceptable

Tumor promotion- rat

2000 ppm dietary up to 8 

weeks

Propiconazole caused proliferative changes, with or without 

pretreatment with an initiator (DENA;nitrosodiethylamine), in the 

rat liver similar to phenobarbital (500 ppm), a known liver tumor 

promoter.
Page 50 of 53

Table A.3 Subchronic, Chronic and Other Toxicity Profile: Propiconazole

Guideline No./ Study 

Type

MRID No. (year)/ 

Classification /Doses

Results

Non- guideline 

Special study

Mechanistic studies: 

Hepatic biochemical 

parameters - Mouse 

45215803 (1998)

Male CD-1 mice, 6/dose 

propiconazole at 0, 850 or 

2500 ppm (0, 149, 578 

mg/kg/day) for 14 days. 

Phenobarbital 850 ppm 

(145 mg/kg/day) to one 

group

Total cytochrome P450 activity increased significantly (3-3.9x of 

the controls) at 850 ppm propiconazole. 7-ethoxyresorufin activity, 

indicative of CYP1A1 induction was increased slightly but not to 

the extent observed following true induction. Lauric acid 

hydroxylation, specifically a result of peroxisome proliferation, was 

not induced by propiconazole. However, the activity of 7-

pentoxyresorufin-O-dealkylase, associated with CYP2B or PB-type 

induction, was clearly increased 30-55-fold by propiconazole. 

Microsomal coumarin 7-hydroxylase, associated with enzymes 

belonging to the subfamily CYP2A was also induced by 

propiconazole treatment consistent with PB-like induction. The 

microsomal activities of epoxide hydrolase and UDPGT and the 

cytosolic activity of GST were slightly increased with 

propiconazole treatment. The pattern of microsomal and cytosolic 

enzyme induction determined biochemically was entirely consistent 

with PB-type induction. Propiconazole resulted in a marked 

increase of total testosterone oxidation. 

The results from the determination of microsomal and cytosolic 

enzyme activities, testosterone hydroxylation, and immunoblot 

analyses show that propiconazole is not a 3-MC or mixed type 

inducer, but causes a pure PB-type induction of cytochrome P450 

activity.

The effects of propiconazole treatment on mouse liver weights and 

liver enzymes were comparable to those produced by phenobarbital, 

a known liver enzyme inducer and liver tumor promoter. The 

authors concluded that propiconazole can thus be considered a 

strong phenobarbital-type inducer of xenobiotic metabolizing 

enzymes in the mouse. 
Page 51 of 53

Table A.3 Subchronic, Chronic and Other Toxicity Profile: Propiconazole

Guideline No./ Study 

Type

MRID No. (year)/ 

Classification /Doses

Results

Non- guideline 

Special study

Mechanistic studies: 

Hepatocellular 

proliferation - Mouse

45215802 (1999)

Male CD-1 mice 40/dose 

propiconazole at 0, 850 or 

2500 ppm (0, 127, 353 

mg/kg/day) for up to 60 

days. A group of 40 mice 

given 850 ppm PB. Five 

mice/group were sacrificed 

on days 1, 2, 3, 4, 7, 28, or 

60 (IP injection of 100 

mg/kg BrdU two hours 

prior to sacrifice)

Test material and Phenobarbital (PB) induced a dose- related 

increase in absolute and relative liver weights. All mice developed 

hepatocellular hypertrophy (primarily in the centrilobular 

hepatocytes with mild effects in the midzonal hepatocytes). Liver 

necrosis and cytoplasmic vacuolation were noted. Increased mitotic 

activity was observed in all groups. Minimal to moderate 

hepatocellular nerosis of hypertrophic single or focal cells was 

found predominately in the high dose and PB group. Treatment 

with propiconazole or PB induced a >1000% increase in BrdUstaining hepatocellular nuclei within 24 hours from the start of the 

study that peaked at a >3600% increase by 48 hours. Thereafter, 

the number of BrdU-stained nuclei decreased dramatically and was 

not biologically different from controls 7 days after the start and 

through the remainder of the study. For all treatment groups, the 

BrdU-staining nuclei were found primarily in the 

centrilobular/midzonal portions of the liver. These data support the 

conclusion that propiconazole induced an initial time- and doserelated proliferation in the liver followed by a sustained treatmentrelated hypertrophy in a manner similar to the known hypertrophic 

agent PB. The hepatomegaly was attributed to a sharp and transient 

induction of hepatocellular proliferation as well as to a time- and 

dose-related increase in the severity of hepatocellular hypertrophy.

Appendix B: EPA Review of Human Research

This risk assessment relies in part on data from studies in which adult human subjects 

were intentionally exposed to a pesticide or other chemical. These studies were determined 

to require a review of their ethical conduct, have received that review and have been 

determined to be ethical.

The PHED Task Force, 1995. The Pesticide Handlers Exposure Database, Version 1.1. Task Force 

members Health Canada, U.S. Environmental Protection Agency, and the National Agricultural 

Chemicals Association, released February, 1995.

The Agricultural Handler Exposure Task Force (AHETF), 2011. The Occupational Handler Unit 

Exposure Surrogate Reference Table. U.S. Environmental Protection Agency. Released June 21, 2011.
Page 52 of 53

Appendix C: Physical and Chemical Properties of Propiconazole

Table 3. Physicochemical Properties of Technical Grade Propiconazole.

Parameter Value Reference

Boiling point 120 C at 1.9 Pa, >250 C at 101.325 kPa MRID No. 43698701

pH 4.9 at 25 C (1% aqueous dispersion) MRID No. 43698701

Density 1.289 g/cm3at 20 C MRID No. 43698701

Water solubility 0.10 g/L at 20 C MRID No. 41720301

Solvent solubility (temperature not specified)

Completely miscible in ethanol, acetone, 

toluene and n-octanol. hexane = 47 g/L MRID No. 42030201

Vapor pressure 4.2 x 10-7 mm Hg at 25 C MRID No. 41720301

Dissociation constant (pKa) 1.09 MRID No. 43698701

Octanol/water partition coefficient Log(KOW) 3.72 at pH 6.6 and 25 C MRID No. 43698701

UV/visible absorption spectrum ( max, nm) Not available MRID No. 40583703

Appendix D: International Residue Limit Status

Propiconazole (122101; 12/8/2011)

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico1 Codex2

40 CFR 180.434:

Plant: propiconazole per se

Livestock: propiconazole per se

Commodity Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico1 Codex

Bean, snap 0.70 

Bean, succulent shelled 0.10 

Legume, foliage 30

Bean, dry seed 0.40

Tomato 3.0 

Fruit, citrus, group 10-10 8.0 

Fruit, stone, group 12, except 

plum

4.0 

Plum 0.60

Citrus oil 1000

Completed: 

1 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.

2

* = absent at the limit of quantitation; Po = postharvest treatment, such as treatment of stored grains. PoP = 

processed postharvest treated commodity, such as processing of treated stored wheat. (fat) = to be measured on the 

fat portion of the sample. MRLs indicated as proposed have not been finalized by the CCPR and the CAC.
Page 53 of 53

E. CHEMICAL NAMES AND STRUCTURES OF METABOLITES

* N

HC

=

=

CH

N

N 

 CH2 C

Cl Cl O O

CH2 CH 

 

CH2 CH CH3 OH

 

N

HC

=

=

CH

N

N 

 CH2 C

Cl Cl O O

CH2 CH 

 

CH2 CH2 OH

 N

HC

=

=

CH

N

N 

 CH2 C

Cl Cl O O

CH2 CH 

 

COOH 

CH2 C

Cl Cl O O

CH2 CH 

 

CH2 COOH 

N

HC

=

=

CH

N

N 

 N

HC

=

=

CH

N

N CH2 C

Cl Cl O

 

N

HC

=

=

CH

N

N 

 CH2 CH

Cl Cl OH

Cl Cl HOOC

N

HC

=

=

CH

N

N 

 CH2 C

Cl Cl O O

CH2 CH 

 

CH2 CH2 CH3 CGA 64250 CGA 118244

CGA 118245 CGA 217495

CGA 217496 CGA 91304

CGA 91305 CGA 177291

APPENDIX: REFERENCE COMPOUNDS