UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

DA TE: December I 0, 2015 

OFFICE OF CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

SUBJECT: Propiconazole: Human Health Risk Scoping Document in Support of Registration 

Review 

PC Code : 12210 I DP Barcode: D429076 

Decision No.: 508972 Registration No: NIA 

Petition No.: None Regulatory Action: Registration Review 

Assessment Type: Scoping Document Case No.: 3 125 

TXR No.: None CAS No.: 60207-90- 1 

FROM: 

MRIDNo.: None 

Thurston Morton, Risk Assessor/Chemist 

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Antimicrobials Division (75 1 OP) 

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Pesticide Re-Evaluation Division (7508P) 

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Sandra O'Neill, Chemica l Review Manager 

Risk Management Branch II (RMBll), AD (7510P) 

Page I of35 
Propiconazole Human-Health Assessment Scoping Document 0429076 

Attached is the Health Effects Division (HED) and Antimicrobials Division (AD) human health 

risk assessment scoping document for propiconazole submitted in support of Registration 

Review. To evaluate the scope of work necessary to support Registration Review, HED and AD 

have considered recent risk assessments for propiconazole, the Human Health Risk Assessment 

for the 2006 Reregistration Eligibility Decision Document (RED), updates to its toxicity, 

exposure and usage databases, and the latest Agency science policy and risk assessment 

methodologies. The most recent HED human health risk assessment for propiconazole was 

conducted in 20 15 (Memo, 12/2/2015, T. Morton, 0426494); the most recent AD human health 

risk assessment for propiconazole was conducted in 2011 (Memo, 8/23/20 11 , T. Leighton, 

0393026). 

Page 2 of 35 
Propiconazole Human-Health Assessment Scoping Document D429076

Page 3 of 35

Executive Summary

Background: 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. Non-food, conventional uses include use on 

commercial, public and residential ornamentals, landscapes and turf. In addition, propiconazole 

is registered for antimicrobial use as a material preservative and wood preservative which will be 

assessed by the Antimicrobial Division (AD). Propiconazole is formulated as a soluble 

concentrate (SC), emulsifiable concentrate (EC), ready-to-use (RTU), water dispersible granule 

(WDG), granular, and flowable concentrate (FlC). The most recent HED human health risk 

assessment was conducted in 2015 (T. Morton, 12/2/2015, D426494); the most recent AD human 

health risk assessment for propiconazole was conducted in 2011(Memo, 8/23/2011, T. Leighton, 

D393026). 

HED and AD evaluated the most recent propiconazole human health risk assessment to 

determine whether sufficient data are available and whether any updates are needed to support 

Registration Review. HED and AD have considered all registered uses for propiconazole with 

respect to its toxicity, exposure, and usage databases, and the most updated Agency science 

policy and risk assessment methodologies to determine the scope of work necessary to support 

Registration Review. The current document pertains only to the Registration Review data 

requirements for propiconazole. 

Hazard Identification/Toxicology: The toxicology database for propiconazole is complete for 

evaluating and characterizing toxicity and selecting endpoints for risk assessment. Based on a 

weight-of-evidence (WOE) approach considering all the available propiconazole hazard and 

exposure information, the HED Hazard and Science Policy Council (HASPOC) concluded that a 

28-day day inhalation study and a subchronic neurotoxicity study are not required at this time 

(TXR # 0056387). In spite of the waiver, the registrant submitted an SCN study with 

propiconazole in December 2013 (MRID 49300503) and was reviewed in 2014 and found 

acceptable (TXR 0056920). HASPOC also waived the requirement for an immunotoxicity study 

for propiconazole (TXR 0056761 and TXR 0056730). The primary target organ for 

propiconazole toxicity in animals is the liver. No new toxicological data are required. The 

Agency does not anticipate the need to revise the toxicological endpoints, points of departure, or 

safety factors for propiconazole during Registration Review.

Residue Chemistry and Dietary Exposure: Adequate metabolism (crops, livestock, and 

rotational crops) and magnitude of the residue data are available to support the registered uses. 

Adequate methods are available for enforcement of the currently established tolerances. No 

additional residue chemistry data are needed to support the currently registered uses. The 

Agency does not anticipate the need for a revised dietary assessment during Registration Review 

unless dietary exposure models or the Estimated Drinking Water Concentrations (EDWCs) are 

updated. Although there are registered antimicrobial uses that could result in indirect food 

contact, including a use on mushroom trays, these uses are expected to result in minimal dietary 

exposure compared to the conventional agricultural uses of propiconazole. Therefore, a dietary 

exposure assessment has not been conducted for the antimicrobial uses of propiconazole. 
Propiconazole Human-Health Assessment Scoping Document D429076

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Residential Exposure: 

Conventional Uses: All registered residential uses for propiconazole (ornamentals, lawns/turf, 

paint) have been reassessed using the 2012 Residential SOPs (J. Miller, D403629, 11/15/12). 

Residential risk estimates were not of concern (i.e., margins of concern [MOEs] > 100). During 

Registration Review, HED anticipates conducting updated residential assessments to incorporate 

required chemical-specific turf transferrable residue (TTR) data. The Agency will examine the 

need for spray drift and volatilization assessments during Registration Review for propiconazole 

based on the potential for exposure to bystanders from agricultural applications.

Antimicrobial Uses: The Agency anticipates using proprietary exposure studies received from 

the post-RED Generic Data Call-In (GDCI) to develop a new exposure assessment. 

Residential handler exposures to propiconazole for paints and wood preservative stains 

(brush/roller and airless sprayer) are anticipated to be assessed, using proprietary data, for 

Registration Review. 

For residential post-application exposure, the Agency will develop a new residential exposure 

assessment for dermal and incidental ingestion exposures for children playing on propiconazole 

treated wood decks or playground structures, using the propiconazole dislodgeable residue data 

(MRID 48825400; e.g., new wood wipe data) received from the post-RED GDCI. 

The Agency anticipates requiring additional exposure data, including an applicator product use 

narrative (Series 875.1700) to clarify use rates and wood retentions, intended antimicrobial uses, 

and application equipment. 

Aggregate Risk Assessment: As part of Registration Review, updated aggregate risk 

assessments may be necessary to reflect revised dietary or residential exposure estimates. 

Occupational Exposure: 

Conventional Uses: The HED occupational exposure database is adequate to support the 

Registration Review for propiconazole. The most recent occupational handler and postapplication exposure assessment did not identify risks of concern. HED does not anticipate the 

need for a revised occupational assessment during Registration Review; however, policy changes 

may occur that require incorporation, as well as inclusion of the required chemical-specific turf 

transferrable residue (TTR) data identified for the residential exposure assessment.

Antimicrobial Uses: The Agency anticipates conducting new occupational exposure 

assessments for registration review to support wood and material preservation uses. 

Occupational exposure assessments are needed based on proprietary exposure data received from 

the post-RED GDCI and new application rates. The Agency anticipates the need to use the new 

proprietary exposure data received from the RED data call-in to assess metalworking, wood 

preservation, paint, and liquid pour exposures for a variety of different material preservative 

uses. In registration review, applicator product use data (875.1700) is needed to clarify uses 

(particularly the use of plastics), application rates (wood retentions), and application equipment 

(verify sapstain and wood pressure treatments).
Propiconazole Human-Health Assessment Scoping Document D429076

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Summary - Risk Assessment Updates, Data Deficiencies, and Label Revisions: Based on the 

current use patterns, there are data deficiencies.

Conventional Use Risk Assessment Updates: 

 Harmonization of tolerances with Codex and Canadian maximum residue limits (MRLs) 

will be evaluated along with tolerance expression revision.

 Revised aggregate risk assessment may be necessary to reflect revised dietary exposure 

estimates, and/or residential exposure estimates. 

 A turf transferable residue (TTR) study (Guideline 875.2100) is anticipated to be required

in order to determine exposure and risk associated with children contacting treated turf. 

A revised residential risk assessment may be necessary.

 The need for a spray drift and volatilization risk assessment for propiconazole will be 

examined during Registration Review.

HED notes that based on the assumptions and resulting risks associated with the currently 

registered uses, it is highly unlikely that revised risk assessments conducted in support of 

Registration Review will yield exposures greater than HED’s level of concern. 

Antimicrobial Use Risk Assessment Updates: 

 New occupational risk assessments will be necessary for metalworking (machinists) and 

wood preservation (sapstain and pressure treatment workers). New occupational risk 

assessments will also be necessary for material preservative exposures, such as airless 

sprayer and paintbrush to paints and stains and liquid pour applications, in a variety of 

material preservative products.

 New residential risk assessments will be necessary to reflect new exposure data for paint 

and stain (airless sprayer and paintbrush) applications.

 New residential post-application risk assessments will be needed for pressure treated 

decks and playsets.

 Revised aggregate risk assessment may be necessary to reflect revised residential 

exposure estimates. 

DETAILED CONSIDERATIONS

Registered Use Patterns

Conventional Uses

Propiconazole is formulated as a soluble concentrate (SC), emulsifiable concentrate (EC), readyto-use (RTU), water dispersible granule (WDG), granular, and flowable concentrate (FlC). The 

maximum application rate is 0.29 lbs ai/A for applications to outdoor agricultural crops, 0.45 lb 

ai/100 gal as a fruit dip, and 2.8 lb ai/A for mushroom houses. The maximum application rate is 

1.8 lbs ai/A for applications to turf. Applications can be made using ground and aerial 

equipment. Propiconazole is a systemic triazole-type fungicide that provides broad spectrum 

disease control on a variety of food and non-food crops. Non-food uses include use on 

commercial, public and residential ornamentals, landscapes and turf.
Propiconazole Human-Health Assessment Scoping Document D429076

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Antimicrobial Uses

Propiconazole is the active ingredient in material preservative products (Use Site Category VII) 

and in wood preservation products (Use Site Category X). As a materials preservative, the 

products are used in items such as metalworking fluids, adhesives, caulks, coatings, stains, 

paints, inks, paper, textiles, canvas (i.e., awnings, boat covers, carpet backing, cordage, tents, 

tarpaulins, and wall coverings), cordage, leather, and leather finishing pastes, fat liquors, or 

finishes. As a wood preservative, the products can be used on green or fresh cut lumber, poles, 

posts, and timbers; manufactured wood products such as logs, wood chips/sawdust, plywood 

veneer, and particle board; dry lumber; and finished wood products such as millwork, shingles, 

shakes, siding, plywood, and structural lumber and composites. 

The majority of the products are intended for use at wood treatment facilities; however, 

propiconazole is also formulated for use in mushroom houses to protect timber trays and benches 

and for use on cooling tower wood. The wood and wood products can be treated through nonpressure treatment methods and pressure treatment methods. The percentage of propiconazole in 

various products can range from 0.1% to 50%. 

Hazard Identification/Toxicology

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

and selecting endpoints for risk assessment. Based on a WOE approach considering all the 

available propiconazole hazard and exposure information, the HASPOC concluded that a 28-day 

day inhalation study and a subchronic neurotoxicity study are not required at this time (TXR # 

0056387). In spite of the waiver, the registrant submitted an SCN study with propiconazole in 

December 2013 (MRID 49300503) and was reviewed in 2014 and found acceptable (TXR 

0056920). HASPOC also waived the requirement for an immunotoxicity study for 

propiconazole (TXR 0056761 and TXR 0056730). 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. There are mixed effects in the 

developmental and reproduction rat studies. In a rat developmental study, fetal effects were 

observed at doses lower than doses at which maternal effects were seen demonstrating 

quantitative evidence of increased susceptibility of fetuses to in utero exposure to propiconazole. 

While in rabbits, developmental toxicity occurred at higher doses than maternally toxic doses. 

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 rat offspring to propiconazole. 

Propiconazole does not appear to be neurotoxic based on acute and subchronic neurotoxicity 

studies. The concern for susceptibility is low since clear NOAELs (No Adverse Effect Level) 

were established in the rat and rabbit developmental studies and the points of departure selected 

for the risk assessment scenarios are protective of the susceptibility observed in the rat 

developmental study. Therefore, the FQPA safety factor was reduced to 1X. 

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. 
Propiconazole Human-Health Assessment Scoping Document D429076

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Endpoints/Points of Departure (PODs) for Risk Assessment. Toxicological endpoints were 

selected for dietary/drinking water, occupational and residential exposure scenarios. Acute and 

chronic points of departure (PODs) were selected for assessment of food and drinking water 

exposures. An acute POD for the general population was selected from an acute neurotoxicity 

study in rats. An acute POD for females 13-49 was selected from a developmental toxicity study 

in rats. A chronic/cancer POD 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 

short-term inhalation, dermal, and incidental oral exposures were selected from the acute 

neurotoxicity study in rats. Toxicological endpoints for intermediate-term incidental oral 

exposure and intermediate- and long-term inhalation and dermal exposures were selected from a 

carcinogenicity study in mice. Since an oral study was selected for dermal exposure, a 40% 

dermal absorption factor (DAF) from a dermal absorption study in rats is used for route to route 

extrapolation. A DAF of 1% and 26.6% for paints and stains, respectively, are used for 

assessment of antimicrobial uses in paints and stains. An uncertainty factor of 100X was applied 

to endpoints selected for all exposure routes (10X for interspecies extrapolation, 10X for 

intraspecies variation). Therefore, the level of concern (LOC) for residential and occupational 

exposure and risk is for margins of exposure (MOEs) less than 100.

FQPA Factor. 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 available in the database with clinical toxicity at the high dose 

only with no microscopic changes. A subchronic neurotoxicity study in rats demonstrated no 

neurotoxic effects (clinical or pathological) at the highest dose tested. 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.

A summary of toxicological doses and points of departure for propiconazole is presented in 

Table 3 in the Appendix. A toxicity profile of propiconazole is presented in Tables 4 and 5, and 

guideline data requirements in Table 6 of the Appendix.

Conclusions for Toxicology

The toxicology database for propiconazole is complete. Based on a WOE approach considering 

all the available propiconazole hazard and exposure information, the HASPOC concluded that a 

28-day day inhalation study is not required at this time (TXR # 0056387).

The Agency does not anticipate the need to revise the toxicological endpoints, points of 

departure, or safety factors for propiconazole during Registration Review.
Propiconazole Human-Health Assessment Scoping Document D429076

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Residue Chemistry and Tolerance Assessment

Propiconazole is registered for use on a large number of food and feed crops. The maximum 

application rate is 0.23 lbs ai/A for applications to outdoor agricultural crops, 0.45 lb ai/100 gal as 

a fruit dip, and 2.8 lb ai/A for mushroom houses. Applications can be made using handheld, bath, 

ground and aerial equipment. 

Permanent tolerances are currently established for the combined residues of propiconazole, 1-

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

metabolites determined as 2,4-DCBA and expressed in parent equivalents, at levels ranging from 

0.1 ppm on numerous plant commodities to 40 ppm in/on grass straw [40 CFR §180.434(a)]. 

Permanent tolerances are also established for the combined residues of propiconazole and its 

metabolites determined as 2,4-DCBA at 0.05 ppm in fat, meat, and meat byproducts (except liver 

and kidney) of livestock, 2.0 ppm in liver and kidney of livestock, and at 0.05 ppm in milk; 

however, no tolerances have been established for eggs and poultry commodities. A time-limited 

tolerance of 10 ppm is currently in effect for avocado [40 CFR §180.434(b)]. In addition, 

tolerances with regional restrictions have been established for combined propiconazole residues 

at 1.0 ppm in/on cranberry and at 0.5 in/on wild rice grain[40 CFR §180.434(c)]. Tolerances 

with inadvertent residues have been established for combined propiconazole residues at 0.1 ppm 

in/on alfalfa forage and alfalfa hay.

Available plant metabolism data (primary and rotated crops) show that plants absorb, metabolize 

and translocate propiconazole throughout the plant. A major metabolic pathway in plants 

appears to be hydroxylation (primarily of the beta-carbon) of the n-propyl group on the 

dioxolane ring of the cis/trans isomers of propiconazole. These metabolites appear to readily 

form sugar conjugates. The majority of Total Radioactive Residue (TRR) was found in the 

stalks, such as peanut stalk, wheat forage and straw, grape leaves, and celery stalks. The nature 

of propiconazole residues in livestock is adequately understood based on acceptable goat and 

poultry metabolism studies. The HED Metabolism Assessment Review Committee (MARC) 

concluded that for plants and livestock, residues of propiconazole and all its metabolites 

containing the 2,4-dichlorophenyl moiety (2,4-DCBA), including conjugates, are of concern and 

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

included in the dietary (water) risk assessments. For tolerance expression, MARC concluded 

that the current tolerance expression for propiconazole should be amended to include residues of 

propiconazole only. For enforcement purpose, the Multiresidue Methods Section 302 (Luke 

Method; Protocol D) detects parent propiconazole.

Adequate crop field trial and processing data are available for all registered crops. There are no 

outstanding issues related to the use directions. Adequate methods are available for enforcement 

of the currently established tolerances in crops and livestock. The FDA PESTDATA database 

(PAM Volume I, Appendix I) indicates that propiconazole is completely recovered (>80%) using 

Multiresidue Methods Section 302. The recovery of propiconazole metabolites CGA-91305, 

CGA-118244, and 1,2,4-triazole is variable using Section 302. Propiconazole and metabolites 

CGA-91305, CGA-118244, and 1,2,4-triazole are not recovered using Multiresidue Methods 

Sections 303 and 304.

Conclusions: The current residue chemistry database is sufficient to support the registered uses; 

no additional residue chemistry data are required. During registration review the tolerance 
Propiconazole Human-Health Assessment Scoping Document D429076

Page 9 of 35

expression will be changed to include parent only as recommended by the MARC. In addition, 

HED is recommending to alter the significant figures in a number of tolerances to conform to

current policy on establishing tolerances at two significant figures. However, the residues of 

concern for risk assessment purposes will remain the same.

Estimated Drinking Water Concentrations (EDWCs)

Conventional Uses:

Propiconazole appears to be persistent and moderately mobile to relatively immobile in most soil 

environments. In the aquatic environment, propiconazole degradation appears to be dependent 

solely on aqueous photolysis in the presence of photo sensitizers. In a soil environment, 

propiconazole dissipation appears to depend on incorporation or binding to soil organic matter 

content. Laboratory and terrestrial field dissipation data indicate that propiconazole is stable in 

soil and aqueous environments. However, in supplemental aquatic dissipation data using basinirrigation and flow through irrigation systems in rice fields, propiconazole was found to be 

dissipated rapidly (t 1/2 < 5 days). Aqueous photolysis studies using sensitizers indicated rapid 

degradation (t 1/2 < 1 days) of propiconazole, which appears to be the case in rice fields. 

Furthermore, aquatic metabolism and dissipation studies indicate propiconazole dissipates by 

incorporation or binding into the organic matter content of soil/sediment. Propiconazole 

mobility in soil appears to be dependent on the soil's organic matter content. In general, 

propiconazole appears to be moderately mobile (Kd < 5) in soils with a low organic matter 

content (< 1 %). However, in soils with higher organic matter content (> I %), propiconazole 

appears to be relatively immobile (Kd > 5). Therefore, propiconazole may reach ground water in 

soils with low organic contents. Propiconazole may also contaminate surface water through offsite runoff and spray drift.

The drinking water residues were provided by the Environmental Fate and Effects Division 

(EFED). in the following memorandum: “Drinking Water Assessment for Proposed New Uses of 

Propiconazole on Dill, Radish, Leafy Brassica Subgroup SB, Watercress, Ti palm and Crop 

Group conversions for Stone Fruit Group 12-12 and Tree Nut Group 14-12.” (I. Abdel-Saheb, 

05/27/15, D423648) and incorporated directly into the most recent dietary assessment. The 

highest estimates from ground water (acute, 37.9 ppb and chronic, 35.1 ppb) are directly entered 

into the exposure model to assess the contributions from drinking water. 

Antimicrobial Uses:

The drinking water exposure assessment conducted for the conventional uses would be expected 

to result in higher potential residues in drinking water than would result from an assessment of 

the antimicrobial uses. Therefore, no drinking water exposure assessment from the antimicrobial 

uses is anticipated to be conducted for the propiconazole registration review.
Propiconazole Human-Health Assessment Scoping Document D429076

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Dietary Exposure

Conventional Uses:

Screening level acute and refined chronic dietary and drinking water exposure and risk 

assessments were recently conducted (T. Morton, D426495, 12/1/2015) using the Dietary 

Exposure Evaluation Model software with the Food Commodity Intake Database DEEM-FCID, 

Version 3.16, which incorporates consumption data from USDA’s National Health and Nutrition 

Examination Survey, What We Eat in America, (NHANES/WWEIA). This dietary survey was 

conducted from 2003 to 2008. 

Conservative acute and refined 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. At the 95th percentile, 

the exposure to the general U.S. population is 26 % of the aPAD; the highest exposed subgroup 

(Children 1-2 yrs old) is 84% of the aPAD. The exposure to the general U.S. population is 8 % 

of the cPAD, and the most highly exposed subgroup (Children 1-2 yrs old) is 25 % of the cPAD. 

A dietary exposure assessment for the free triazole or conjugated triazoles was also recently 

updated (T. Morton, D426492, 4/9/15). 

Antimicrobial Uses:

EPA has not established tolerances or tolerance exemptions for residues for the antimicrobial 

uses of propiconazole. Propiconazole has not been cleared as a food additive by the US Food and 

Drug Administration (US FDA) under the Federal Food, Drug, and Cosmetic Act (FFDCA) 

Section 409 (including the antimicrobial uses on paper and plastic). 

Although there are registered antimicrobial uses that could result in indirect food contact, 

including a use on mushroom trays, these uses are expected to result in minimal dietary exposure 

compared to the conventional agricultural uses of propiconazole. There is also an existing 

tolerance for residues in/on mushrooms based on the conventional use pattern, which will 

adequately account for any potential residues due to the antimicrobial use. Additionally, the 

conventional agricultural uses of propiconazole do not result in dietary exposure risks of 

concern. Therefore, a dietary exposure assessment has not been conducted for the antimicrobial 

uses of propiconazole.

Conclusions for Dietary Exposure

The Agency does not anticipate the need for a revised dietary assessment during Registration 

Review unless dietary exposure models or the Estimated Drinking Water Concentrations 

(EDWCs) are updated.
Propiconazole Human-Health Assessment Scoping Document D429076

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Residential Exposure

Conventional Uses

All registered residential uses for propiconazole (ornamentals, lawns/turf, paint) have been 

reassessed using the 2012 Residential SOPs (J. Miller, D403629, 11/15/12). There is potential 

for both handler (dermal and inhalation) and post-application (dermal and incidental oral) 

exposures. Residential risk estimates were not of concern (MOEs are > 100), with the lowest 

handler MOE of 500 resulting from application to turf using a hose-end sprayer; the lowest postapplication MOE of 100 resulted from combined dermal and incidental oral exposure for 

children (1 to <2 years old) contacting treated turf.

In conjunction with the 2007 40 CFR Part 158 Data Requirements, HED typically requires

submission of a turf transferable residue (TTR) study in order to determine exposure and risk

associated with contacting treated turf. The estimated residential turf post-application exposure

using default TTR values for propiconazole is not minimal in comparison to the level of concern. 

The calculated MOE is not greater than 10 times higher than the level of concern, with the lowest

combined MOE = 100 compared to the LOC of 100. Future refinements of this post-application

exposure for propiconazole are anticipated in order to incorporate new TTR data and to

incorporate any advances in EPA risk assessment methodology. Therefore, EPA is requiring the

40CFR TTR data to facilitate any necessary exposure assessment refinements and to further

EPA’s general understanding of the availability of turf transferable pesticide residues.

Residential bystander exposures resulting from off-site transport (e.g., spray drift or

volatilization) may occur as a result of applications of propiconazole. The potential for spray

drift will be quantitatively evaluated for each pesticide during the Registration Review process

which ensures that all uses for that pesticide will be considered concurrently. This document

outlines the quantification of indirect non-occupational exposure to drift. In terms of

volatilization, the Agency has developed a Volatilization Screening Tool and a subsequent

Volatilization Screening Analysis (http://www.regulations.gov/#!docketDetail;D=EPA-HQOPP-2014-0219). During Registration Review, the Agency will utilize this analysis to determine

if data (i.e., flux studies, route-specific inhalation toxicological studies) or further analysis is

required for propiconazole. 

Antimicrobial Uses

 

Residential handler dermal and inhalation exposures to propiconazole are anticipated to be 

assessed for the application of treated paints and stains. The residential exposure scenarios 

applicable to this use include applicator brush/roller and airless sprayer. The Agency will likely 

use brush/roller data submitted from the Antimicrobial Exposure Assessment Task Force (II) 

from the RED data call in, but the Agency anticipates needing product use information for paints 

and stains for registration review (875.1700). The Agency does not anticipate assessing postapplication/bystander inhalation exposures and MOEs for use of paints (vapor exposure to adults 

and children) since the vapor pressure is low (e.g., <1E-6 mm Hg). 

Wood products commercially treated with end use products containing propiconazole may be 

used for decks and children’s play sets, and therefore, residential post-application exposure 

concerns may exist for dermal and incidental ingestion routes. Based on the potential concerns 
Propiconazole Human-Health Assessment Scoping Document D429076

Page 12 of 35

from the past assessment, the Agency required wipe studies (Series 875.2300) in the RED to 

measure residues from treated decks at the highest wood retention rate for propiconazole. The 

Agency received an acceptable residue study from the RED Data Call-in (D405090). However, 

the agency also anticipates the need to require product use (875.2700) information to clarify the 

maximum retention rate for wood preservative uses in registration review.

On March 8, 2006, the Agency published a Federal Register Notice announcing receipt of a 

request to cancel apparel, furnishings (except shower curtains), and carpet fiber applications of 

propiconazole and EPA issued cancellation orders for these uses on May 26, 2006. However, the 

Agency has identified some product labels that still have these uses. EPA is working with 

registrants to remove these uses; therefore, the apparel, furnishings (except shower curtains), and 

carpet fiber uses will not be considered in registration review.

Conclusions of Residential Exposure Assessment

Conventional Uses: During Registration Review, HED anticipates updating the residential 

assessments to reflect incorporation of the required chemical-specific TTR data. The need for 

spray drift and volatilization risk assessment for propiconazole will also be examined during 

Registration Review.

Antimicrobial Uses: AD anticipates needing new product use information (875.1700) for handler 

exposures from paints and stains in registration review. AD also anticipates needing new 

product use information (875.2700) to clarify exposures and retention rates of wood preservative 

used to treat decks and playsets. AD will likely use proprietary handler exposure data submitted 

from the RED data call-in for paints and stains and proprietary post-application wood residue 

data submitted from pressure treated wood decks and playsets to conduct updated assessments. 

Aggregate Risk Assessment

Currently, aggregate risks from propiconazole are not of concern. For adults, the short-term 

residential dermal MOE estimated from post-application activity on treated turf, when 

aggregated with dietary exposure, is 200, which does not fall below the LOC of 100 and is 

therefore not of concern. For children, the aggregated MOE (incidental oral + dermal + dietary) 

MOE was 96 [note that while this falls below HED’s LOC of 100, this assessment is considered 

conservative since the short-term endpoints are based on a conservative LOAEL (Lowest 

Observed Adverse Effect Level) that is 3x higher than the NOAEL. Further, the assessment it is 

based on a combination of tolerance-level residues and reliable data on average field trial 

residues and 100 PCT (percent crop treated), conservative assumptions in the ground and surface 

water modeling, and conservative assumptions to assess post-application exposure of children as 

well as incidental oral exposure of toddlers. Additionally, the assessment could be further refined 

by using PCT estimates and anticipated residues for all crops. Accordingly, even though this 

MOE for children 1-2 years old is slightly below the target MOE of 100, the difference is small 

and is more than offset by the conservative exposure assumptions and therefore not of concern. 

Specifically, it aggregates the short-term risk for toddlers from incidental oral, dermal, and food 

and water (as a background). This short-term aggregate assessment is considered very 

conservative in that the residential incidental oral post-application exposure was calculated by 

combining screening level assessments (which by themselves already have conservative 

estimates). The chronic dietary exposure estimate is based on average field trial residues, 
Propiconazole Human-Health Assessment Scoping Document D429076

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tolerance level residues and 100 percent crop treated. The highest average percent crop treated 

reported by BEAD in the April 2015 SLUA was 55%. In addition, the scenarios for hand to 

mouth activity on turf and turf high contact activity dermal exposure both use conservative 

default assumptions. A turf transferable residue study is unavailable but being requested from 

the registrant for registration review of propiconazole. In all probability this study will reduce 

exposure estimates for both of these pathways. The only scenario that is expected to result in 

potential intermediate-term exposure to propiconazole is post-application exposure to children 

from wood treatment, which is from an antimicrobial use. However, this scenario is likely to be 

refined based on newly submitted dislodgeable wood residue data received from the RED data 

call-in. 

The previous aggregate triazole human health risk assessment was recently updated for free 

triazoles and its conjugates and the aggregate estimates remain below HED’s level of concern (T. 

Morton, D426493, 4/9/15).

Conclusions:

As part of Registration Review, updated aggregate risk assessments are anticipated to be needed

to reflect revised dietary or residential exposure estimates.

Occupational Exposure

Conventional Uses

Occupational handler and post-application exposures are expected based on the registered uses of 

propiconazole. Propiconazole is currently formulated as liquid (emulsifiable, soluble, and 

flowable concentrates packaged as “mix-your-own” and “ready-to-use” (RTU) products) and 

wettable powder in water-soluble packets (WP/WSP). Applications are made by air, 

groundboom, chemigation, airblast, post-harvest treatment equipment, seed piece dip, tree 

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

Application rates vary depending upon the crop or use-site, but range from 0.112 pounds active 

ingredient per acre (lb ai/A) to 0.225 lb ai/A for agricultural crops, 0.37 lb ai/A for ornamentals, 

and 1.8 lb ai/A for turf. Occupational exposure scenarios applicable to propiconazole range from 

short-term (1 to 30 days) to intermediate-term (30 days to six months) duration. 

The occupational handler assessments indicate that, for the registered uses, all of the potential

exposure scenarios provide combined (dermal + inhalation) margins of exposure (MOEs) greater

than or equal to the LOC of 100 at some level of personal protection and/or engineering control

(K. O’Rourke, D428502, 08/16/15). The labels for most uses require chemical-resistant gloves

in addition to baseline clothing attire of long pants, long sleeved shirt and shoes plus socks.

Several levels of postapplication exposure activities have been identified ranging from “low”

activities such as weeding and scouting in immature plants to very high exposure activities such

as harvesting or thinning fruit from trees. Adequate dislodgeable foliar residue (DFR) data have 

recently been submitted for peaches (MRID 44959701) and are not likely to alter the conclusions 

of the previous assessments; additional DFR data are not needed at this time. Using default DFR

residue estimates, the short- and intermediate-term postapplication assessments indicate that the
Propiconazole Human-Health Assessment Scoping Document D429076

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MOEs reach the LOC of 100 on the day of application for all use scenarios. The restricted entry

interval (REI) listed on the applicable labels is 12 hours, which is adequately protective.

Antimicrobial Uses

For wood preservatives, occupational workers are exposed to propiconazole wood preservatives 

during wood treatment activities such as dip treatment, double vacuum, and pressure treatment, 

and remedial uses such as applying wood stains using a brush/roller and/or airless sprayer on 

decks. In addition, occupational workers could potentially become exposed through the dermal 

and inhalation routes from material preservatives from pouring liquids or from mists and vapors 

during metalworking applications (e.g., machinists).

New inhalation exposure data from Park, 2009 will be used to assess inhalation exposure for the 

machinist assessment. Dermal exposure will use assumptions from the 2-hand immersion model 

from ChemSTEER.

Handler exposure data were required in the post-RED GDCI to assess dermal and inhalation

exposure to workers. Specifically, dermal exposure data (Guidelines 875.1100 and 875.1200)

was required for painters (brush/roller and airless sprayer) and workers handling treated wood

(pressure and non-pressure uses). Inhalation exposure data (Guidelines 875.1300 and 875.1400)

was required for painters (brush/roller and airless sprayer) and workers handling treated wood

(pressure and non-pressure uses). These data are still needed to assess post-application dermal

and incidental ingestion risks associated with children contacting pressure treated wood decks or

playsets. Since these data are outstanding, surrogate proprietary data can be used to conduct 

dermal and inhalation routes of exposure and assess both handler and post-application activities 

of wood preservatives (dip and spray sapstain treatments, and pressure treatments). Surrogate 

proprietary unit exposure data generated by the Antimicrobial Exposure Assessment Task Force 

II (AEATF) and Sapstain Industry Group (SIG) could be used for these wood treatment

assessments. Both the AEATF and SIG require compensation for the proprietary use of their unit 

exposure data. Surrogate proprietary unit exposure data generated by the AEATF can also be 

used to assess material preservatives (machinists and liquid pour) and the paint and wood stain 

uses (brush/roller and airless sprayer). 

The duration of exposure for most of the occupational uses is believed to be best represented by 

the short (1 to 30 days) and intermediate-term (30 days to 6 months) durations since workers are 

expected to engage in work for longer durations. For the wood preservation and machinist use, 

the Agency anticipates long-term durations.

Conclusions:

Conventional Uses

The occupational exposure database is adequate to support the Registration Review process. 

Based on a review of the registered labels and the most recent risk assessment, HED previously 

conducted occupational handler assessments for the occupational handler scenarios anticipated 

for the registered uses of propiconazole. HED does not anticipate the need for a revised 

occupational assessment during Registration Review; however, policy changes may occur that 
Propiconazole Human-Health Assessment Scoping Document D429076

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require incorporation, as well as inclusion of the required chemical-specific turf transferrable 

residue (TTR) data identified for the residential exposure assessment. 

Antimicrobial Uses

AD anticipates the need to conduct new occupational exposure assessments for registration 

review to support wood and material preservation uses. Occupational exposure assessments are 

needed based on proprietary exposure data received from the RED data call in and new 

application rates. The Agency will use new proprietary exposure data anticipated from the postRED GDCI to assess metalworking, wood preservation, paint, and liquid pour exposures for a 

variety of different material preservative uses. For registration review, AD anticipates the need to 

require product use data (875.1700) to clarify uses (particularly the use of plastics), application 

rates (wood retentions), and application equipment (verify sapstain and wood pressure 

treatments).

Public Health, Pesticide Epidemiology, and Human Incidence Data

For this evaluation, both the OPP Incident Data System (IDS) and the Centers for Disease 

Control and Prevention/National Institute for Occupational Safety and Health (CDC/NIOSH) 

Sentinel Event Notification System for Occupational Risk-Pesticides (SENSOR) databases were 

consulted for pesticide incident data on the active ingredient propiconazole (S. Recore, 9/15/15, 

D429078). The purpose of the database search is to identify potential patterns in the frequency 

and severity of the health effects attributed to. Propiconazole is not included in the AHS, and, 

therefore, this study does not provide information for this report.

Based on the relatively low frequency and severity of incident cases reported for propiconazole 

in both IDS and SENSOR-Pesticides there does not appear to be a concern at this time that 

would warrant further investigation. The Agency will continue to monitor the incident 

information and if a concern is triggered, additional analysis will be included in the risk 

assessment.

International Harmonization

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

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

parent and all tolerances converted to parent only. This will be done at the time of the 

registration review risk assessment.

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

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

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

Mexican MRLs are expressed in terms of propiconazole. The Canadian MRLs are expressed in 

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

moiety. At this time, the U.S. tolerance expression is harmonized with Canada but not Codex. 

Once the tolerance expression is changed to propiconazole only, the tolerance expression will be 

harmonized with Codex. 
Propiconazole Human-Health Assessment Scoping Document D429076

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Attachment F is a summary of the Canadian, Mexican, and Codex maximum residue limits 

(MRLs) for residues of propiconazole. As part of registration review, HED will reevaluate the 

Canadian, Mexican, and Codex MRLs and harmonize when possible. 

Cumulative 

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.

Human Studies 

The 2006 RED as well as the 2012 and 2015 risk assessments relied in part on data from studies 

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

data, which include studies from PHED 1.1; the AHETF database; the Outdoor Residential 

Exposure Task Force (ORETF) database; and the ARTF database, are (1) subject to ethics 

review pursuant to 40 CFR 26, (2) have received that review, and (3) are compliant with 

applicable ethics requirements. For certain studies, the ethics review may have included review 

by the Human Studies Review Board. Descriptions of data sources, as well as guidance on their 

use, can be found at the Agency website1. 

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.epa.gov/compliance/resources/policies/ej/exec_order_12898.pdf. The Office of 

Pesticide Programs (OPP) typically considers the highest potential exposures from the legal use 

of a pesticide when conducting human health risk assessments, including, but not limited to, 

people who obtain drinking water from sources near agricultural areas, the variability of diets 

within the U.S., and people who may be exposed when harvesting crops. Should these high 

 

1 http://www.epa.gov/pesticides/science/handler-exposure-data.html and 

http://www.epa.gov/pesticides/science/post-app-exposure-data.html
Propiconazole Human-Health Assessment Scoping Document D429076

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exposures indicate potential risks of concern, OPP will further refine the risk assessments to 

ensure that the risk estimates are based on the best available information.

Risk Assessment Updates and Data Deficiencies

The risk assessment updates that may be required under Registration Review are summarized 

below. 

The following data deficiencies were identified: 

 Toxicology: The toxicology database for propiconazole is complete. 

 Residue Chemistry: None

 ORE: 

o For conventional uses: A turf transferable residue (TTR) study (Guideline

875.2100) is required in order to determine exposure and risk associated with

children contacting treated turf.

o For antimicrobial uses: AD will need product use (Guideline 875.1700) data for

handlers of paints and stains to clarify use rates. AD will also need product use

(Guideline 875.2700) data to clarify exposures retention rates for wood

preservatives used to treat decks and playsets.

EPA anticipates the following risk assessment updates during Registration Review:

 Toxicology: the Agency does not anticipate the need to revise the toxicological 

endpoints, points of departure, or safety factors for propiconazole during Registration 

Review. 

 Dietary Exposure: The Agency does not anticipate the need for a revised dietary 

assessment during Registration Review unless dietary exposure models or the Estimated 

Drinking Water Concentrations (EDWCs) are updated.

 Residue Chemistry: Update the tolerance expression.

 Aggregate Exposure: As part of Registration Review, updated aggregate risk 

assessments may be necessary to reflect revised dietary or residential exposure estimates. 

 Occupational/Residential Exposure:

o For conventional uses: Revised occupational/residential risk assessment may be 

necessary to reflect the submitted TTR data as well as need for spray drift and 

volatilization risk assessment.

o For antimicrobial uses: New occupational risk assessments will be necessary for 

worker exposure to the following antimicrobial uses:

- metalworking (machinists),

- wood preservation (sapstain and pressure treatment workers),

- painting and staining (airless sprayer and paintbrush applications), and

- material preservatives (liquid pour applications).

o New residential risk assessments will be necessary to for paint and stain (airless 

sprayer and paintbrush) applications. 
Propiconazole Human-Health Assessment Scoping Document D429076

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Attachment A: References

Attachment B: Chemical Identity and Physicochemical Properties

Attachment C: Toxicological Endpoint Selection Table

Attachment D: Hazard Profile Table

Attachment E: Guideline Data Requirements

Attachment F: International Residue Limits
Propiconazole Human-Health Assessment Scoping Document D429076

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Attachment A: References 

Author Barcode/TXR # Date Title

S. Recore D429078 9/15/15 Propiconazole: Tier I (Scoping) Review of Human

Incidents and Epidemiology

T. Morton D426494 12/1/15 Propiconazole Human Health Risk Assessment for the 

New Uses of Propiconazole on dill, leafy brassicas crop 

subgroup 5B, ti palm, watercress, and quinoa, along with 

expansion to fruit, stone, group 12-12; except plum, and 

nut, tree, group 14-12.

T. Morton D426495 12/1/15 Propiconazole: Acute and Chronic Aggregate Dietary 

(Food and Drinking Water) Exposure and Risk 

Assessments for the New Use of Propiconazole on Dill, 

Crop subgroup 5B Leafy Brassica greens, Radish, Ti 

Palm, Watercress, and the Expansion of Fruit, stone, 

group 12-12, and Nut, tree, group 14-12.

K. O’Rourke D428502 8/16/15 Propiconazole. Occupational and Residential Exposure 

Assessment for Proposed New Uses on Dill, Brassica 

Leafy Greens, Radish, Ti Palm, Watercress, Stone Fruit, 

and Tree Nuts.

T. Morton D426492 & 

D426496

4/9/15 Common Triazole Metabolites: Updated Dietary (Food + 

Water) Exposure and Risk Assessment to Address The 

New Section 3 Registrations For Use of Propiconazole on 

Tea, Dill, Mustard Greens, Radish, and Watercress; Use of 

Difenoconazole on Globe Artichoke, Ginseng and 

Greenhouse Grown Cucumbers and Conversion of the 

Established Foliar Uses/Tolerances for Stone Fruit and 

Tree Nut Crop Groups to Fruit, Stone, Group 12-12 and 

the Nut, Tree, Group 14-12.; and Use of Flutriafol on 

Hops.

T. Morton 426493 & 

426497

4/9/15 Common Triazole Metabolites: Updated Aggregate 

Human Health Risk Assessment to Address The New 

Section 3 Registrations For Use of Propiconazole on Tea, 

Dill, Mustard Greens, Radish, and Watercress; Use of 

Difenoconazole on Globe Artichoke, Ginseng and 

Greenhouse Grown Cucumbers and Conversion of the 

Established Foliar Uses/Tolerances for Stone Fruit and 

Tree Nut Crop Groups to Fruit, Stone, Group 12-12 and 

the Nut, Tree, Group 14-12.; and Use of Flutriafol on 

Hops.

James S Miller D403629 & 

406831

11/15/12 Propiconazole: Assessment of Aerial; Chemigation; and 

Groundboom Applications to Sugarcane and Cereal Grains 

(Wheat; Barley; Oats; Rye, and Triticale).

James S Miller D390250 2/16/12 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).

Y. Donovan D329668 6/28/06 Propiconazole: Phase 4, HED Chapter of the Reregistration Eligibility Decision Document (RED).

Y. Donovan D329394 06/15/06 Propiconazole (122101): Reregistration Eligibility 

Decision (RED) Document; Revised Residue Chemistry 

Considerations

T. Leighton D324052 2/1/06 Revised Occupational and Residential Exposure 

Assessment of the Antimicrobial Uses to Support the 

Reregistration Eligibility Decision (RED) Document. 
Propiconazole Human-Health Assessment Scoping Document D429076

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J. Tao D365243 11/23/09 Propiconazole: Toxicological Review and Dermal 

Absorption Factor Determination for the Proposed Increase 

in Application Rate for Use in Paints and Stains.

N. Mottl D64956 4/21/10 Propi-Shield and WocosenTM: Occupational and Residential 

Exposure Assessment for a Proposed Product with Non-Food 

New Antimicrobial Uses (emulsions, adhesives, binders, latex 

paints, plastics and plastic coatings) of Propiconazole Proposed 

Products

T. Leighton D393026 8/23/11 Propiconazole: Update of the Paint and Stain Risk 

Assessment based on New Dermal Absorption Data.

N. Mottl D405090 3/13/14 Review of the Study: “Determination of Dislodgeable 

Propiconazole Residues from Spruce and Southern Yellow 

Pine (SYP) Boards Pressure Treated with Formulation 

AWP-0911-4”
Propiconazole Human-Health Assessment Scoping Document D429076

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Attachment B.

Nomenclature of Propiconazole

Compound

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 

Chemical structure of 

1,2,4-Triazole (1,2,4-T)

Chemical structure of 

Triazolylalanine (TA)

Chemical structure of

Triazolylacetic acid (TAA)

Physicochemical Properties of Technical Grade Propiconazole.

Parameter Value Reference

Boiling point 120 C at 1.9 Pa, >2500 C at 101.325 

kPa MRID No. 43698701

pH 4.9 at 250 C (1% aqueous dispersion) MRID No. 43698701

Density 1.289 g/cm3at 200 C MRID No. 43698701

Water solubility 0.10 g/L at 200 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 250 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 250 C MRID No. 43698701

UV/visible absorption spectrum (8max, 

nm) Not available MRID No. 40583703

N

N N

O

O

Cl

Cl

HN

N

N

N

N

N

HO

NH2

O

N

N

N

HO

O
Propiconazole Human-Health Assessment Scoping Document D429076

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Attachment C:

Summary of Toxicological Doses and Endpoints for Propiconazole for Use in Dietary Human Health Risk Assessments 

Exposure/

Scenario

Point of 

Departure

Uncertainty/F

QPA 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 MRID 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 MRID 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 carcinogenicity study on CD-1 mice. 

MRID 00129918

LOAEL = 50 mg/kg/day based on nonneoplastic liver effects (increased liver weight 

in males and increase in liver lesions: 

masses/raised areas/ swellings/nodular areas 

mainly). 

Incidental Oral 

short-term (1-30 

days)

NOAEL= 

30 

mg/kg/day

UFA= 10X

UFH=10X

Residential LOC 

for MOE = 100

Occupational LOC 

for MOE = 100

Acute Neurotoxicity Study-Rats MRID 

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).

Incidental Oral 

Intermediate-term 

(1-6 months)

NOAEL= 

10 

mg/kg/day 

UFA= 10X

UFH=10X

Residential LOC 

for MOE = 100

Occupational LOC 

for MOE = 100

24 Month carcinogenicity Study - Mice MRID 

00129918

LOAEL = 50 mg/kg/day based on nonneoplastic liver effects (increased liver weight 

in males and increase in liver lesions: 

masses/raised areas/ swellings/nodular areas 

mainly).

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 MRID 

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).

Dermal 

Intermediate Term 

(1-6 months) and 

Long Term (>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 carcinogenicity Study - Mice MRID 

00129918

LOAEL = 50 mg/kg/day based on nonneoplastic 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 MRID 

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).
Propiconazole Human-Health Assessment Scoping Document D429076

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Summary of Toxicological Doses and Endpoints for Propiconazole for Use in Dietary Human Health Risk Assessments 

Exposure/

Scenario

Point of 

Departure

Uncertainty/F

QPA Safety 

Factors

RfD, PAD, LOC 

for Risk 

Assessment

Study and Toxicological Effects

Inhalation 

Intermediate Term

(1-6 months) and 

Long Term (>6 

months)

NOAEL= 

10 

mg/kg/day

24 Month carcinogenicity Study - Mice MRID 

00129918

LOAEL = 50 mg/kg/day based on nonneoplastic 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, TXR No. 

0009771

* DAF of 1% and 26.6% were used for paints and stains, respectively.

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

DAF = Dermal Absorption Factor 

Propiconazole Acute Toxicity Profile: February 2015

Guideline 

No.

Study Type MRID # Results Toxicity 

Category

870.1100 Acute Oral Toxicity– rat 00058591 (1978) LD50 =1517 mg/kg III

870.1200 Acute Dermal Toxicity-rabbit 00058596 (1979) LD50 = >4000 mg/kg III

870.1300 Acute Inhalation Toxicity– rat 41594801 (1988) LC50 = >5.84 mg/L IV

870.2400 Acute Eye Irritation 00058597 (1978) Corneal opacity reversed in 72 hrs III

870.2500 Acute Dermal Irritation 00058598 (1978) No irritation IV

870.2600 Skin Sensitization 44949501 (1999) dermal sensitizer -
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Attachment D:

Subchronic, Chronic and Other Toxicity Profile: Propiconazole: February 2015

Guideline No./ Study 

Type

MRID No. (year)/

Classification /Doses

Results

870.3100

90-Day Feeding 

Study in Rat

00058606 (1979)

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. 

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) 

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

870.3465 28/90-

Day Inhalation

Waived per HASPOC TXR 0056387 

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
Propiconazole Human-Health Assessment Scoping Document D429076

Page 25 of 35

Subchronic, Chronic and Other Toxicity Profile: Propiconazole: February 2015

Guideline No./ Study 

Type

MRID No. (year)/

Classification /Doses

Results

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 

(laboratory historical control incidence: was 0/5431). This 

confirms findings of cleft palate noted in above study (MRID 

40425001).

Severe clinical toxicity in the treated animals (ataxia, coma, 

lethargy, prostration, 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)

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). 

NOAEL = 100 ppm (10 mg/kg/day).

Liver tumors at 2500 ppm in male mice.
Propiconazole Human-Health Assessment Scoping Document D429076

Page 26 of 35

Subchronic, Chronic and Other Toxicity Profile: Propiconazole: February 2015

Guideline No./ Study 

Type

MRID No. (year)/

Classification /Doses

Results

870.4200

18 - month 

carcinogenicity 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

870.6200b 

90-Day Neurotoxicity 

Screening Battery 

(rat)

49300503 (2014)

Acceptable/guideline

♂ 0, 200, 600, or 3500 ppm 

0,13, 38, and 222 mg/kg 

bw/day, 

♀ 0, 200, 600, or 1500 ppm 

0, 15, 45, and 111 mg/kg 

bw/day, 

LOAEL in males = 3500 (220 mg/kg/day) based on significant 

reductions in body weight gain and food consumption

NOAEL in males = 600 ppm (38 mg/kg/day).

NOAEL in females = 1500 ppm (111/kg/day), the highest dose 

tested.

LOAEL in females was not established.

870-5100

Bacterial reverse 

mutation

00058601 (1979)

Unacceptable

25-2025 μg/plate

Negative in Salmonella strains with or without S-9 activation. Test 

material purity not specified, not tested up to cytotoxic dose.

870-5300

In vitro cell 

transformation assay 

(BALB/3T3)

00133349 (1982)

Acceptable/guideline

1.16-18.5 μg/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
Propiconazole Human-Health Assessment Scoping Document D429076

Page 27 of 35

Subchronic, Chronic and Other Toxicity Profile: Propiconazole: February 2015

Guideline No./ Study 

Type

MRID No. (year)/

Classification /Doses

Results

870-5575

Mitotic gene 

conversion assay 

(Saccharomyces 

cerevisiae)

00133343 (1982)

Acceptable/guideline 

10, 30, 90 or 270 μg/ml

No increase in convertants or revertants (did not induce mutation) 

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.

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. The metabolic 

profile of both urine and feces appear to be similar except for the 

presence of parent material in the feces while the urine had 

conjugated phenolic metabolites.

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%
Propiconazole Human-Health Assessment Scoping Document D429076

Page 28 of 35

Subchronic, Chronic and Other Toxicity Profile: Propiconazole: February 2015

Guideline No./ Study 

Type

MRID No. (year)/

Classification /Doses

Results

870.7600

Dermal penetration

(Rat)

47736503 (2008)

Acceptable/guideline

Propiconazole (99.0% 14C at 

the triazole-[3,5] position) in a 

commercial latex paint or

alkyd stain solutions

0.45, 1.6, or 4.5 mg [14C]-

propiconazole/kg

(corresponding to 0.1, 0.35, or 

1.0% [14C]-propiconazole 

prepared in latex paint or 

alkyd stain [w/w]) 

A dermal absorption factor (DAF) of 1% and 26.6% was 

determined following 10-hour exposure of propiconazole for 

commercial paints and stains, respectively.

870-7800

Immunotoxicity

MRID 48799701, 2012

Waiver Request

Waived (TXR 0056761 and TXR 0056730).

Non- guideline 

Special study 

00151517 (1984)

Acceptable/non-guideline

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.

Non- guideline 

Special study

Mechanistic studies: 

Hepatic biochemical 

parameters - Mouse 

45215803 (1998)

Acceptable/non-guideline

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 

-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. 
Propiconazole Human-Health Assessment Scoping Document D429076

Page 29 of 35

Subchronic, Chronic and Other Toxicity Profile: Propiconazole: February 2015

Guideline No./ Study 

Type

MRID No. (year)/

Classification /Doses

Results

Non- guideline 

Special study

Mechanistic studies: 

Hepatocellular 

proliferation - Mouse

45215802 (1999)

Acceptable/non-guideline

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 necrosis 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.
Propiconazole Human-Health Assessment Scoping Document D429076

Page 30 of 35

Attachment E:

Guideline Data Requirements: Propiconazole: February 2015

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 (non-rodent)

870.3200 21-Day Dermal

870.3250 90-Day Dermal

870.3465 28/90-Day Inhalation

yes

yes

yes

no

waived*

yes

yes

yes

-

-

870.3700a Developmental Toxicity (rodent)

870.3700b Developmental Toxicity (non-rodent)

870.3800 Reproduction

yes

yes

yes

yes

yes

yes

870.4100a Chronic Toxicity (rodent)

870.4100b Chronic Toxicity (non-rodent)

870.4200a carcinogenicity (rat)

870.4200b carcinogenicity (mouse)

870.4300 Chronic/carcinogenicity

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

yes

-

870.7485 General Metabolism

870.7600 Dermal Penetration

870.7800 Immunotoxicity

yes

yes

waived**

yes

yes

-

* waived per HASPOC TXR 005638

** waived per HASPOC TXR 0056761 and TXR 0056730.
Propiconazole Human-Health Assessment Scoping Document D429076

Page 31 of 35

Attachment F:

Propiconazole (122101)

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico1 Codex2

40 CFR 180.434:

Plant/Livestock: combined residues 

of the fungicide 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

1-[[2-(2,4-diclorophenyl)-

4-propyl-1,3-dioxolan-2-

yl]

methyl]-1H-1,2,4-triazole, 

including all metabolites

containing the 2,4-

dichlorophenyl-1-methyl

substituted moiety

Plant and animal 

commodities: 

propiconazole

The residue is fat 

soluble.

Commodity Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico1 Codex2

§180.434 (a) (1)

Almond, hulls 7.0

Banana 0.2 0.2 bananas, plantains 0.1

Barley, bran 6.0

Barley, grain 3.0 0.05 0.2

Barley, hay 30

Barley, straw 20 8 barley straw and 

fodder, dry 

Bean, dry seed 0.40 0.1 0.07 soybean, dry

Bean, snap 0.70 

0.25 edible podded ( 

jackbeans, 

moth beans, runner beans, 

snap beans, soybeans, 

sword beans, wax beans, 

yardlong beans)

Bean, succulent 

shelled 0.10 

0.05 succulent shelled 

(broad beans, cowpeas, 

lima beans)

Beet, garden, roots 0.30 0.3

Beet, garden, tops 5.5 5.5

Beet, sugar, dried pulp 1.0

Beet, sugar, molasses 1.5 1.5

Beet, sugar, roots 0.3 0.3 0.02 sugar beet

Beet, sugar, tops 10

Bushberry, subgroup 

13-07B 1.0 11.3 lingonberries

0.3 cranberry

Caneberry, subgroup 

13-07A 1.0 1

Carrot, roots 0.25 0.25

Cattle, fat 0.05

0.05 0.01 (*) mammalian 

fats (except milk fats) 

(proposed)

Cattle, kidney 2.0 2 0.5 edible offal 

Cattle, liver 2.0 2 (mammalian) 
Propiconazole Human-Health Assessment Scoping Document D429076

Page 32 of 35

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico1 Codex2

Cattle, meat 0.05

0.05 0.01 (*) meat (from 

mammals other than 

marine mammals) 

Cattle, meat 

byproducts, except 

liver and kidney

0.05

0.05

Cilantro, leaves 13 

Citrus, oil 1000 1000

Corn, field, forage 12

Corn, field, grain 0.2 0.2 0.05

Corn, field, stover 30

Corn, pop, grain 0.2 02 0.05

Corn, pop, stover 30

Corn, sweet, forage 6.0

Corn, sweet, kernel 

plus cob with husks 

removed

0.1

0.2 0.05

Corn, sweet, stover 30

Fruit, citrus, group 10-

10 8.0 

8 9 Po oranges, sweet, 

sour (including 

orange-like hybrids): 

several cultivars

Fruit, stone, group 12, 

except plum 4.0 

4 

1 plums

5 peach Po

0.6 plums including 

prunes Po

Goat, fat 0.05 0.05 0.01 (*) mammalian 

fats (except milk fats) 

Goat, kidney 2.0 2 meat byproducts of goats 0.5 edible offal 

Goat, liver 2.0 (mammalian) 

Goat, meat 0.05

0.05 0.01 (*) meat (from 

mammals other than 

marine mammals) 

Goat, meat byproducts, 

except liver and kidney 0.05 2 meat byproducts of goats 0.5 edible offal (mammalian)

Grain, aspirated 

fractions 110

Grass, forage 0.5

Grass, hay 0.5

Grass, straw 40

Hog, kidney 0.2 0.1 meat byproducts of 

hogs

0.5 edible offal 

Hog, liver 0.2 (mammalian) 

Horse, fat 0.05 0.05 0.01 (*) mammalian 

fats (except milk fats)

Horse, kidney 2.0 2 meat byproducts of 

horses

0.5 edible offal 

Horse, liver 2.0 (mammalian)

Horse, meat 0.05

0.05 0.01 (*) meat (from 

mammals other than 

marine mammals)

Horse, meat 

byproducts, except 

liver and kidney

0.05

2 meat byproducts of 

horses

0.5 edible offal 

(mammalian)

Leaf petioles subgroup 

4B 5.0 5
Propiconazole Human-Health Assessment Scoping Document D429076

Page 33 of 35

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico1 Codex2

Low growing berry 

subgroup 13-07G, 

except cranberry

1.3

1.3 

Milk 0.05 0.03 0.01 (*)

Mushroom 0.1 0.1

Nut, tree, group 14 0.1 0.1 0.02 (*) pecan

Oat, forage 4.0

Oat, grain 3.0 0.05

Oat, hay 15

Oat, straw 10 8 oat straw and fodder, 

dry 

Onion, bulb subgroup 

3-07A 0.2 0.2

Onion, green, 

subgroup 3-07B 9.0 9

Parsley, fresh leaves 13 13

Parsley, dried leaves 35 35

Peanut 0.2 0.2

Peanut, hay 20

Peppermint, tops 10.0 10

Pineapple 4.5 4.5 0.02 (*)

Pineapple, process 

residue 7.0 0.02 (*)

Pistachio 0.1 0.1

Plum 0.60 1 0.6 plums including 

prunes Po

Rapeseed subgroup 

20A 0.30 0.02 rapeseeds (canola) 0.02 rapeseed

Rice, bran 15 15

Rice, grain 7.0 7

Rice, hulls 20

Rice, straw 18

Rye, bran 0.6

Rye, forage 9.0

Rye, grain 0.3 0.05 0.02

Rye, straw 10 15 rye straw and 

fodder, dry

Sheep, fat 0.05 0.05 0.01 (*) mammalian 

fats (except milk fats)

Sheep, kidney 2.0

2 meat byproducts of sheep 0.5 edible offal 

(mammalian) 

(proposed)

Sheep, liver 2.0

Sheep, meat 0.05

0.05 0.01 (*) meat (from 

mammals other than 

marine mammals) 

Sheep, meat 

byproducts, except 

liver and kidney

0.05

2 meat byproducts of sheep

Sorghum, grain, forage 12

Sorghum, grain, grain 3.5 3.5

Sorghum, grain, stover 15
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Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico1 Codex2

Soybean, forage 11

Soybean, hay 30 5 soya bean fodder 

Soybean, seed 2.0 0.25 dry soybeans 0.07 soya bean (dry)

Spearmint, tops 10.0 10

Sugarcane, cane 0.4 0.02 (*)

Tomato 3.0 3 3 Po

Vegetable, foliage of 

legume, group 7 30 

Wheat, bran 0.6

Wheat, forage 15

Wheat, grain 0.3 0.05 0.02 wheat, triticale

Wheat, hay 30

Wheat, straw 20 15 wheat and triticale 

straw and fodder, dry

MRLs with No US Equivalent

Coffee beans 0.02

Eggs 0.05 0.01 (*)

Asparagus 0.1

Buckwheat 0.05

Dry (field peas, pigeon 

peas)

0.1

Edible-podded (dwarf 

peas, peas, pigeon 

peas, snow peas, sugar 

snap peas)

0.25

Fat of poultry 0.05

Meat of hogs 0.05

Meat of poultry 0.05

Pearl millet 0.05

Proso millet 0.05

Succulent shelled 

(English peas, garden 

peas, green peas, peas, 

pigeon peas, 

Teosinte 0.05

§180.434 (b) Section 18 emergency exemptions

Avocado

Expiration date 

12/31/16

10

§180.434 (c) Tolerances with regional registrations

Cranberry 1.0 1.3

Rice, wild, grain 0.5 0.5

§180.434 (d) Indirect or inadvertent residues

Alfalfa, forage 0.1

Alfalfa, hay 0.1

Recently proposed

Dill, fresh 30

Dill, dried 80

Dill, seed 15

Leafy Brassica Greens, 

crop subgroup 5B

20
Propiconazole Human-Health Assessment Scoping Document D429076

Page 35 of 35

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico1 Codex2

Radish, tops 0.203

Radish, roots 0.043

Ti palm, leaves 10

Ti palm, roots 0.30

Watercress 6.0

Fruit, stone, group 12-

12; except plum

4.0 4 apricots, fresh prune 

plums, nectarines, peaches, 

plumcots, sweet cherries, 

tart cherries

5 peach Po

0.6 plums (including 

prunes) Po

Nut, tree, group 14-12 0.10 0.1 tree nuts 0.02 pecan (*)

Recently proposed under §180.434 (a) 2 (parent only)

Tea, dried 4.0 4 tea (dried leaves)

Completed: M. Negussie; 09/14/15

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.

3Tolerances are established for residues of propiconazole, including its metabolites and degradates, in or on the 

commodities in the table below. Compliance with the tolerance levels specified below is to be determined by 

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