UNITED STATES ENVIRONMENT AL PROTECTION AGENCY 

MEMORANDUM 

Date: 29-0CT-2015 

WASHINGTON, D.C. 20460 

OFFICE OF 

CllEMICALSAFETY ANO 

POLLUTION PREVENTION 

SUBJECT: Cyproconazole. Scoping Document in Support of Registration Review For 

Human Health Risk Assessment. 

PC Code: 128993 

Decision No.: 50~'175 

Petition No.: NIA 

DP Barcode: 0429084 

Registration No.: NIA 

Regulatory Action: Registration Review Scoping Document 

Risk Assessment Type: NI A Case No.: 7011 

TXR No.: NIA CAS No.: 94361-06-5 

MRID No.: NIA 40 CFR: § 180.485 

FROM: 

.

George F. Kramer, Ph.D., Senior Chemi~ L ~ Anwar Y. Dunbar, Ph.D., Pharmacologist · • ~ 

Joshua G. Godshall, Biologist QrRisk Assessment Branch I (RA.Bf) 

Health Effects Division (HED, 7509P) 

Jenny Tao, Senior Toxicolog·st C. , A_.:.~ ' 

Nathan Mott!, Biologist /'.J1.v/1~.,.ll i"IJ,il f 

Risk Assessment Science Support Branch (RASSB) 

Antimicrobials Division (AO, 751 OP) 

THROUGH: Charles Smith, Branch Chief, RAB 

RABl/HED (7509P) 

Steven Weiss, Branch Chief 

Timothy Leighton, Senior Scientist 

RASSBIAD (7510P) 

TO: Miguel Zavala, Chemical Review Manager 

Pesticide Re-Evaluation Division (PRD) (7508P) 

Rachel Ricciardi, Chemical Review Manager 

Antimicrobials Division (AD, 751 OP) 

Attached is HED's and AD's human health risk assessment scoping document for cyproconazole 

to support Registration Review. 

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Table of Contents 

Executive Summary ........................................................................................................................ 3 

1.0 Introduction .............................................................................................................................. 5 

2.0 Hazard Characterization/ Assessment.. ..................................................................................... 5 

3.0 Residue Chemistry ................................................................................................................... 6 

4.0 Dietary Exposure .................................... ............................................... .................................. 7 

5.0 Residential Exposure ............................................................................................................... 8 

6.0 Aggregate-Risk Assessment .................................................................................................... 9 

7.0 Occupational Exposure ............................................................................................................ 9 

8.0 Public Health and Pesticide Epidemiology Data ................................................................... 11 

9.0 Tolerance Assessment and International Harmonization ...................................................... 13 

10.0 Environmental Justice .......................................................................................................... 13 

11.0 Cumulative ........................................................................................................................... 13 

12.0 Human Studies ..................................................................................................................... 14 

13 .0 Risk Assessment Updates, Data Deficiencies, and Label Revisions .............. ..................... 14 

14.0 References ........ ~ ............................................................................. ...................................... 15 

Attachment I: Chemical Identity Table ....................................................................................... 17 

Attachment 2: Cyproconazole Endpoint Selection Tables (from 2012 Risk Assessment) .......... 19 

Attachment 3: Cyproconazole Acute. Subchronic, and Chronic Toxicity Profile ....................... 21 

Attachment 4: Summary of Registered Uses ............................................................................... 26 

Attachment 5: Cyproconazole International Residue Limit Status Sheet .................................... 27 

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Executive Summary

HED and AD have prepared a scoping document to support Registration Review of the broadspectrum triazole (Group 3) fungicide cyproconazole. Cyproconazole is currently registered as a 

post-emergence foliar applied fungicide to corn (field, and seed), cereals (wheat and triticale), 

soybeans, and peanuts. Several products are registered, all of which are suspension concentrate

(SC) formulations. The most recent HED human health risk assessment was performed in 2012

for the use of cyproconazole on peanuts (D399957, S. Levy et al., 03-OCT-2012). There are 

currently no pending PRIA actions for cyproconazole. 

AD registered a new antimicrobial cyproconazole product as a composite wood preservative in 

2015. The new AD product (EPA Reg. 72616-9) contains 4.5% cyproconazole and 45% 

triadimefon. All other antimicrobial products for this active ingredient have been voluntarily 

cancelled by the registrant, and there are no other pending PRIA actions for cyproconazole.

HED and AD have evaluated the status of the human health assessments for cyproconazole to 

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

Registration Review. HED and AD have considered all available data and human health risk 

assessments for cyproconazole 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 toxicity database for cyproconazole is complete and adequate to support Registration 

Review requirements. No new data are required. For Registration Review, points of departure 

(PODs) and uncertainty/safety factors (UF/SFs) for cyproconazole will be re-evaluated as 

appropriate.

The residue chemistry database for cyproconazole is adequate to support current Registration 

Review data requirements. Adequate metabolism (crops, livestock, and rotational crops), storage 

stability, magnitude of the residue, and processing data are available to support the registered 

uses. Adequate methods are available for enforcement of the currently established tolerances. 

The dietary-exposure database for cyproconazole is adequate to support current registration 

requirements. The most recent risk assessment provided unrefined acute and chronic dietary 

(food + drinking water) exposure estimates that are below HED’s level of concern (LOC) for the 

general U.S. population and all population subgroups. Acute dietary (food + drinking water) risk 

estimates were <100% population-adjusted dose (aPAD) at the 95th percentile of the exposure; 

females 13 to 49 years old were the population with the greatest risk (32% aPAD). Chronic 

dietary (food + drinking water) risk estimates were <100% chronic population-adjusted dose 

(cPAD); all infants (<1 years old) were the most highly exposed population (28% cPAD). A 

chronic cancer dietary assessment was not conducted since it was determined that cyproconazole 

is not a possible human carcinogen. HED notes that the 2012 acute and chronic dietary 

assessments did not incorporate ground water estimated drinking water concentrations (EDWCs) 

modeled using the Pesticide Root Zone Model for GroundWater (PRZM-GW). The impacts of 

using this model to estimate ground water concentrations of cyproconazole will need to be 

considered during Registration Review. As part of Registration Review, a revised dietaryexposure analysis may be required to reflect the most recent dietary-exposure models, potential

revised EDWCs (specifically, use of PRZM-GW), and/or revised toxicological PODs.

There are no proposed or registered products containing cyproconazole at this time that would 
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result in residential exposure. Therefore, a residential handler and post-application exposure 

assessment is not currently required for Registration Review.

In accordance with the Food Quality Protection Act (FQPA), HED must consider and aggregate 

(add) pesticide exposures and risks from three major sources: food, drinking water, and 

residential exposures. Because there are no residential uses for cyproconazole, only food and 

water were included in previous aggregate assessments. There is sufficient information available 

to assess aggregate exposure; however, a new aggregate risk assessment may be required during 

Registration Review to incorporate revised dietary exposure analyses and/or toxicological PODs. 

Application of cyproconazole also results in potential exposures to the metabolites T (1,2,4-

triazole), TA (triazolylalanine), TAA (triazolylacetic acid), and THP (triazolyl hydroxypropionic 

acid). These compounds are considered to be toxicologically different from cyproconazole. 

HED recently conducted an aggregate risk assessment for these compounds with the resulting 

exposure estimates less than HED’s level of concern (D426493, T. Morton, 09-APR-2015). As 

part of Registration Review, a revised triazole risk assessment may be required. 

Revised occupational handler and post-application exposure and risk assessments are needed for 

the conventional uses during Registration Review to account for recent changes in exposure 

assessment assumptions, including body weight, amount treated, and transfer coefficients (TCs). 

AD recently conducted an occupational and residential assessment for the only registered

cyproconazole label on 09-SEP-2015 (D428952). No data or additional assessments were 

required in this risk assessment. AD did not conduct an occupational handler risk assessment 

since the label specifically restricts applications to closed loading systems. Additionally, 

residential exposure was not applicable since the wood uses specified on the label were for

engineered and composite wood that is not used to manufacture decks and playsets.

The Agency will examine the need for spray drift and volatilization assessments during 

Registration Review for cyproconazole based on the potential for exposure to bystanders from 

agricultural applications.

No data deficiencies were identified for cyproconazole. EPA notes the following risk assessment 

updates will need to be completed during Registration Review:

o Toxicology: 

o Re-evaluation of PODs and UF/SFs.

o Residue Chemistry/Dietary Exposure: 

o A revised dietary-exposure analysis may be required to reflect the most recent 

dietary-exposure models, potentially revised EDWCs (specifically, use of PRZMGW), and/or revised toxicological PODs and UF/SFs.

o Occupational/Residential Exposure: 

o Revised occupational handler and post-application risk assessments will be 

necessary for the conventional uses of cyproconazole to reflect the most recent 

HED policies and/or toxicological PODs and UF/SFs. 

o Spray drift and bystander assessments may be necessary to reflect current HED 

policies.

o Aggregate Exposure: 

o Revised aggregate exposure analyses may be required to reflect revised dietary 

exposure estimates and/or changes to the toxicological PODs and UF/SFs.
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1.0 Introduction

HED has prepared a scoping document to support Registration Review of the broad-spectrum 

triazole (Group 3) fungicide cyproconazole. Cyproconazole is a mixture of two distereoisomers 

(2RS,3RS:2RS,3SR; ~1:1) and acts by inhibiting sterol biosynthesis in fungi. It is effective for 

the control of several plant diseases, such as yellow Sigatoka (Mycosphaerella musicola) and 

black Sigatoka (Mycosphaerella fijiensis var. difformis) in bananas, early leaf spot (Cercospora 

arachidicola) and stem rot (Sclerotitum rolfsii) in peanuts, and rust (Puccinia spp.) and powdery 

mildew (Erysiphe spp.) in wheat and soybean. Several products are registered, all of which are 

SC formulations. The most recent human health risk assessment was performed in 2012 and was 

for the use of cyproconazole on peanuts (D399957, S. Levy et al., 03-OCT-2012). There are 

currently no pending PRIA actions for the conventional uses of cyproconazole.

AD has only one registered antimicrobial product of cyproconazole and one use, which is a

composite wood preservative for structural lumber that contains 4.5% cyproconazole and 45% 

triadimefon. AD recently conducted an occupational and residential assessment for this label on 

09-SEP-2015 (D428952).

2.0 Hazard Characterization/Assessment

Consistent with other triazole-fungicides (e.g., tetraconazole), the most sensitive mammalian 

toxicological effects for cyproconazole following oral exposure occur in the liver. At higher 

doses greater than those causing liver toxicity, increased macrophages in the lung, increased 

white blood cell counts and globulins were observed through both the oral and dermal routes. 

Additionally, increased hemosiderin deposition in the spleen of females and evidence of thyroid 

hypertrophy of the follicular epithelium were observed only through the dermal route.

There was no evidence of increased susceptibility following in utero exposure to rats. There was 

no evidence of offspring toxicity in the two-generation reproduction toxicity study. In the 

prenatal developmental toxicity study in rabbits, there was evidence of an increased quantitative 

fetal susceptibility, such that malformations were seen at a dose below maternal toxicity. 

However, there are no residual uncertainties for pre and/or post-natal toxicity since: 1) Clear noobserved adverse-effect levels (NOAELs) were established for the observed fetal effects and; 2) 

The POD is used for acute dietary risk assessment for the most sensitive population and are 

protective of the prenatal susceptibility. 

Cyproconazole is not acutely toxic through the oral, dermal, and inhalation routes (Toxicity 

Category III). It is neither an ocular nor a dermal irritant (Toxicity Category IV). 

Cyproconazole did not cause dermal sensitization. 

The endpoints presented in Attachment 3 are from the most recent risk assessment for 

cyproconazole (D399957, S. Levy et al., 03-OCT-2012). As part of Registration Review, the 

PODs and UF/SFs for cyproconazole will be re-evaluated as appropriate. Using a weight-ofevidence approach, HED’s Hazard Science and Policy Council (HASPOC) determined that acute 

and subchronic neurotoxicity studies, immunotoxicity, and subchronic inhalation studies are not 

required at this time (K. Rury et al., TXR# 0052355, and J. Bever et al., TXR# 0057282). The 

hazard profile table containing all of the currently reviewed data is presented in Attachment 2. 

Conclusions: The toxicity database for cyproconazole is complete and adequate to support 
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Registration Review requirements. No new data are required. For Registration Review, PODs and 

UF/SFs for cyproconazole will be re-evaluated as needed/appropriate.

3.0 Residue Chemistry

Cyproconazole is currently registered to Syngenta Crop Protection for use on peanuts, soybeans, 

and cereal grains. Permanent tolerances are established for the free and conjugated residues of 

the fungicide cyproconazole, α-(4-chlorophenyl)-α-(1-cyclopropylethyl)-1H-1,2,4-triazole-1-

ethanol, in or on imported green coffee beans, aspirated grain fractions, field corn raw 

agricultural commodities (RACs), peanut RACs, soybean RACs, wheat RACs, the fat and meat 

byproducts of cattle, goat, horse and sheep [40 CFR §180.485(a)(1)]. A tolerance is established 

for the combined free and conjugated residues of cyproconazole and its metabolite [δ-(4-

chlorophenyl)-β,δ-dihydroxy-γ-methyl-1H-1,2,4-triazole-1-hexenoic acid in or on milk [40 CFR 

§180.485(a)(2)]. In addition, tolerances are established for the combined free and conjugated 

residues of cyproconazole and its metabolite 2-(4-chlorophenyl)-3-cyclopropyl-1-[1,2,4]triazol1-yl-butane-2,3-diol, in or on the liver of cattle, goat, horse and sheep [40 CFR §180.485(a)(3)]. 

The nature of cyproconazole residues in plants is adequately understood for purposes of 

currently registered crops. For purposes of establishing tolerances and risk assessment, the 

residues of concern are free and conjugated cyproconazole (D352237, M. Rust-Clock et al., 02-

MAY-2008). The nature of cyproconazole residue in livestock is adequately understood. Based 

on the available ruminant metabolism data and the results of the dairy cattle feeding study, HED 

concluded that the residues of concern for the tolerance expression and risk assessment in milk 

are cyproconazole (free and conjugated) and metabolite M36. In liver, the residues of concern 

for the tolerance expression and risk assessment are cyproconazole (free and conjugated) and 

Metabolite M14. In meat, meat byproducts (except liver), and fat; the residues of concern for the 

tolerance expression and risk assessment are free and conjugated cyproconazole (D352237, M. 

Rust-Clock et al., 02-MAY-2008).

HED has also determined that T, TA, TAA, and THP are also potential residues of concern in 

plants and livestock for all triazole fungicides. However, these triazole-related residues will not 

be regulated for specific triazole pesticides, but will be evaluated for the entire class of triazole 

compounds. Issues related to T, TA, TAA, and THP are addressed in a separate document 

(D426493, T. Morton, 09-APR-2015). 

An adequate gas chromatograph/nitrogen-phosphorus detection (GC/NPD) method is available 

for enforcing tolerances of cyproconazole (free and conjugated) on plant commodities (Method 

AM-8022-0994-3). Syngenta has also submitted a copy of a method (Method AM-0842-0790-

0), which is essentially identical to the current tolerance enforcement method, except that it 

includes the option for analysis by either NPD or mass-selective detection (MSD). The validated 

method limit of quantitation (LOQ) is 0.01 ppm. LC-MS/MS method (Syngenta Method RAM 

499/01) is adequate for enforcement for residues cyproconazole in livestock commodities. The 

method has also undergone a successful ILV trial and radiovalidation. Syngenta has provided 

LC/MS/MS enforcement methods for the determination of residues of M14 in liver (Method 

GRM033.03A), and for the determination of residues of M36 in milk (Method GRM033.02A). 

HED has determined these methods are suitable as enforcement methods as defined in Standard 

Operating Procedure (SOP) No. ACB-019 (9/15/08).
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Multiresidue Method testing data for cyproconazole were submitted and forwarded to FDA. The 

1/94 FDA PESTDATA database (PAM Volume I) indicates that residues of free cyproconazole 

are completely recovered (>80%) using multiresidue method Sections 302, but are not recovered 

using Sections 303 and 304.

Adequate field trial and processing data are available to support all registered uses of 

cyproconazole. An adequate number of trials were conducted in the appropriate geographical 

regions using the appropriate formulations applied at the maximum use rates. These studies are 

also supported by adequate storage stability data and processing data. Adequate magnitude of 

the residue data in livestock are also available. 

The previously submitted confined/limited field rotational crop trial data reflecting a total 

application rate of 0.073 lb ai/A/season are adequate, and support the rotational crop restrictions 

on the current labels. Primary crops may be replanted immediately, if crop is lost. Cotton and 

cereal grains other than wheat can be planted 180 days after last application. All other crops 

(including leafy vegetables) can be planted 270 days after last application.

Analytical standards for cyproconazole (expiration date 4/30/2017) and metabolites M14 (2-(4-

chlorophenyl)-3-cyclopropyl-1-[1,2,4]triazol-1-yl-butane-2,3-diol; expiration date 12/31/2016) 

and M36 (δ-(4-chlorophenyl)-β,δ-dihydroxy-γ-methyl-1H-1,2,4-triazole-1-hexenoic acid; 

expiration date 12/31/2016) are currently available in the National Pesticide Standards 

Repository (personal communications with Theresa Cole, 9/1/15 and 9/14/15). 

Conclusions: The residue chemistry database is adequate to support current Registration Review 

data requirements. Adequate metabolism (crops, livestock, and rotational crops), storage 

stability, magnitude of the residue, and processing data are available to support the registered 

uses. Adequate methods are available for enforcement of the currently established tolerances. 

4.0 Dietary Exposure

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

assessments were conducted for cyproconazole using the Dietary Exposure Evaluation Model 

software with the Food Commodity Intake Database (DEEM-FCID) Version 3.16, which uses 

food consumption data from the U.S. Department of Agriculture’s National Health and Nutrition 

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

conducted from 2003 to 2008. The acute and chronic analyses were performed to support a 

Section 3 request on peanuts. The unrefined acute and chronic analyses assumed tolerance-level 

residues, 100% crop treated (CT), and DEEM (ver. 7.81) default processing factors. EDWCs 

were incorporated directly into DEEM-FCID under the food categories “water, direct, all 

sources” and “water, indirect, all sources.” Tier 1 EDWCs from surface water were estimated 

using the FQPA Index Reservoir Screening Tool (FIRST) (Version 1.1.1) and EDWCs in ground 

water were estimated using the Screening Concentration In Ground Water model (SCI-GROW) 

(Version 2.3). Since the EDWC estimates from surface water were higher than those from 

groundwater, EDWC estimates in surface water were used in both acute and chronic dietary risk 

assessments. 

An acute dietary risk analysis was conducted only for females 13-49 years old since an endpoint 

of concern attributable to a single dose for general population was not identified. The resulting 

acute (food + drinking water) risk estimate for female 13-49 years old was 32% of the aPAD at 

the 95th percentile of the exposure distribution; i.e., below HED’s LOC (<100% aPAD). 
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Therefore, the acute dietary exposure to cyproconazole is not of concern to HED. 

The resulting chronic (food + drinking water) risk estimates were less than HED’s LOC (<100% 

of the cPAD) for U.S. general population (13% of the cPAD) and all population sub-groups; the 

most highly exposed population subgroup was all infants (<1 years old) at 28% of the cPAD. 

Therefore, the chronic dietary exposure to cyproconazole is not of concern to HED. A chronic 

cancer dietary assessment was not conducted since it was determined that cyproconazole is not a 

possible human carcinogen. 

HED notes that the 2012 acute and chronic dietary assessments did not incorporate ground water 

EDWCs modeled using PRZM-GW. The impacts of using this model to estimate ground water 

concentrations of cyproconazole will need to be considered during Registration Review. 

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

uses of cyproconazole. Cyproconazole has not been cleared as a food additive by the US Food 

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

Section 409. There are no currently registered antimicrobial uses that could result in direct or 

indirect food contact. Therefore, these uses are not expected to contribute to the dietary 

exposure for the conventional agricultural uses of cyproconazole (i.e., direct treatment to 

growing crops intended for human or livestock consumption). Additionally, the conventional 

agricultural uses of cyproconazole do not result in dietary exposure risks of concern. Therefore, 

a dietary exposure assessment has not been conducted for the antimicrobial uses of 

cyproconazole. 

Conclusions: The dietary-exposure database is adequate to support current registration 

requirements. In the most recent risk assessment, chronic dietary exposures were not of concern 

to HED. However, as part of Registration Review, a revised dietary-exposure analysis may be 

required to reflect the most recent dietary-exposure models and potential revised EDWCs

(specifically, use of PRZM-GW) and/or revised toxicological PODs.

5.0 Residential Exposure

There are no proposed or registered conventional or antimicrobial products containing 

cyproconazole at this time that would result in residential exposure. Therefore, a residential 

handler and post-application exposure assessment is not currently required for Registration 

Review.

AD does not expect residential post-application exposure to decks or play sets (D428952). The 

engineered and wood composite uses on the label include oriented strand board, waferboard, 

fiberboard, particleboard, plywood, laminated veneer lumber (LVL), and parallel-strand lumber 

(PSL). These types of wood products are most useful for interior construction uses, such as Ijoist framing, and structural beams, but also have outdoor construction uses. LVL is used in both 

bearing and non-bearing walls, as planks, beams, headers, door and window frames, sliding door 

rails, steps, as well as in the roof trusses; PSL is used for load bearing posts and beams. AD 

anticipates that homebuilders would not use this wood to construct wood decks or playground 

structures. AD expects limited dermal post-application contact to children. Drywall would 

prevent dermal contact from many of the interior wood structural uses. Dermal exposure to the 

types of outdoor wood uses listed on the label (e.g., doorframes, posts, beams, and windowsills) 

would be minimal. Inhalation exposure is negligible based on the low vapor pressure of 

cyproconazole (less than 1 x 10-6 mm Hg).
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Non-Occupational Spray Drift Exposure and Risk Estimates: Residential bystander exposures 

resulting from off-site transport (e.g., spray drift or volatilization) may occur as a result of 

applications of cyproconazole. 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. The approach is outlined in the revised (2012) 

Standard Operating Procedures For Residential Risk Assessment (SOPs) – Residential Exposure 

Assessment Standard Operating Procedures Addenda 1: Consideration of Spray Drift. 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 cyproconazole.

Conclusions: There are no proposed or current registrations for products containing 

cyproconazole that allow residential use. Therefore, residential handler and post-application 

exposure assessments will not be needed during Registration Review. The need for spray drift 

and volatilization risk assessment for the conventional uses of cyproconazole will be examined 

during Registration Review.

6.0 Aggregate-Risk Assessment

The most recent aggregate-risk assessment was performed in conjunction with the 2012 HED 

human health risk assessment (D399957, S. Levy et al., 03-OCT-2012). The Agency conducts 

aggregate exposure assessments by summing dietary (food and water) and residential exposures. 

Since there are no registered/proposed uses of cyproconazole that result in residential exposure, 

the acute and chronic aggregate risk assessments are equal to the acute dietary and chronic 

dietary estimates (food and water only), respectively. Short-, intermediate-, and long-term 

aggregate-risk assessments were not performed because there are no registered or proposed uses 

of cyproconazole that result in residential exposures. A cancer aggregate-risk assessment was 

not performed because cyproconazole is classified as “not likely” to be carcinogenic to humans.

Application of cyproconazole also results in potential exposures to the metabolites T, TA, TAA, 

and THP. These compounds are considered to be toxicologically different from cyproconazole. 

HED recently conducted an aggregate risk assessment for these compounds with the resulting 

exposure estimates less than HED’s level of concern (D426493, T. Morton, 09-APR-2015). As 

part of Registration Review, a revised triazole risk assessment may be required. 

Conclusions: There is sufficient information available to assess aggregate exposure. However, 

new aggregate risk assessments may be required during Registration Review to incorporate 

revised dietary exposure estimates and/or toxicological PODs. 

7.0 Occupational Exposure

Cyproconazole is currently registered as a fungicide in post-emergence foliar applications to 

cereal grains, soybeans, and peanuts. Cyproconazole is registered as an engineered and

composite wood-based product. There are no existing pressure-treated antimicrobial woodpreservative products. There is potential for short- and intermediate-term occupational exposure 

to cyproconazole during handling (mixing, loading, and applying) and post-application activities.
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Previous conventional assessments (D322542, M. Clock-Rust, 07-OCT-2005; D330711, K. 

Lowe, 06-SEP-2007; D400184, J. Tyler, 03-OCT-2012) estimated exposure for various 

occupational handler scenarios and found no risks of concern. Based on existing registrations, 

the previous assessments identified the anticipated occupational handler and post-application 

exposure scenarios, so no additional scenarios need to be included in Registration Review. 

Additionally, since the previous reviews, there have been several updates to HED’s exposure 

policies, including updates to default exposure data used for handler scenarios and assumptions 

for body weights (Registration Review will need to consider these updates).

A previous antimicrobial assessment (D428952, T. Dole, 09-SEP-2015) estimated exposure for a 

wood product use and concluded that a quantitative risk assessment was not needed for 

occupational handlers or post application exposures since the label specifically restricts 

applications to closed loading systems. Since this is a recent action, no additional risk 

assessments are anticipated in registration review.

Occupational Handler Exposure/Risk Estimates

The registered cyproconazole labels require occupational handlers to wear long-sleeved shirts, 

long pants, shoes, socks, and chemical-resistant gloves. Applications can be made using 

groundboom, aerial, and chemigation equipment. The updated occupational exposure 

assessment policies and body-weight assumptions were incorporated into the peanut 

cyproconazole exposure assessment and all current occupational handler margins of exposure

(MOEs) for peanuts are not of concern (MOE >100) (D400184, J. Tyler, 03-OCT-2012). 

However, updated assessments will be needed for occupational handlers of cyproconazole for the 

treatment of corn, cereals, and soybeans due to the updated occupational exposure policies. 

AD considered that the potential for occupational dermal and inhalation exposure during the 

mixing and loading of cyproconazole into the processes used to manufacture engineered and 

composite wood products are expected to be negligible since closed loading and delivery 

systems are required. AD does not typically conduct occupational handler risk assessments and 

considers data waivers for low vapor pressure chemicals if the label specifically restricts 

applications to closed loading systems (78 FR 26935).

Occupational Post-Application Exposure/Risk Estimates

Occupational post-application short- and intermediate-term dermal exposures are possible for 

workers contacting treated crops. The MOEs in the most recent occupational post-application 

exposure assessment for peanuts are not of concern (MOE >100) and it incorporated the updated 

exposure assessment policies utilizing changes in TCs and body weight assumptions (D400184, 

J. Tyler, 03-OCT-2012). Therefore, an updated occupational post-application exposure 

assessment will only be required for the cyproconazole uses on cereal grains and soybeans 

during Registration Review. 

AD does not intend to conduct a post-application exposure assessment in registration review.

Occupational dermal post-application exposures from the use of cyproconazole in engineered 

and composite wood products are not expected. AD considers the occupational post-application 

inhalation exposures to cyproconazole as a vapor is to be minimal based on the low vapor 

pressure of cyproconazole (less than 1 x 10-6 mm Hg).

Dislodgeable Foliar Residue (DFR): In accordance with 40 CFR 158, DFR data are required for 

all occupational (e.g., crop, nursery, greenhouse use sites) or residential (e.g., ornamental and 
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vegetable gardens, pick-your-own farms, retail tree farms) uses that could result in postapplication exposure to foliage. In the absence of chemical-specific DFR data, EPA uses default 

values. The 2012 Standard Operating Procedures for Residential Pesticide Exposure 

Assessment includes an analysis of a number of DFR studies, which resulted in the selection of a 

revised default value for the fraction of the application rate available for transfer after a foliar 

application (FAR). These values are based on an analysis of 19 DFR studies. Since that time, the 

Agricultural Re-entry Task Force (ARTF) has submitted information (MRID 49299201) that 

corrects an application rate error made in the original submission of “ARF039 – Determination 

of Dermal and Inhalation Exposure to Reentry Workers During Chrysanthemum Pinching in a 

Greenhouse” (EPA MRID 45344501). As a result, the range of FAR values was revised from 2% 

- 89% to 2% - 47%. In the data, a large range of transferability is observed and this variability 

can potentially be attributable to many factors such as active ingredient; formulation; field 

conditions in the studies; weather conditions (e.g., humidity); or many other difficult to quantify 

factors. Although witnessed across multiple chemicals, this range in FAR values is not expected 

when considering DFR data for a single chemical. At this time, the ARTF submission did not 

alter the selection of 25% as the reasonable, high-end default value. Because DFR data are not 

available for cyproconazole, EPA is using the default value of 25%. Although there may be a 

small degree of uncertainty in the use of the default DFR value for cyproconazole (i.e., there is a 

small chance that the FAR value may exceed the applicable default value), it is likely that the 

health-protective aspects of EPA’s occupational post-application assessment methodology will 

more than compensate for this potential uncertainty. For example, when assessing residential 

and occupational post-application exposure to gardens and ornamentals, EPA assumes the 

following: exposures occur to zero-day (i.e., day of application ) residues every day of the 

assessed exposure duration (i.e., EPA assumes that no dissipation or degradation occurs, it 

doesn’t rain, etc); individuals perform the same post-application activities performed in the TC

study day after day (e.g., weeding, harvesting, pruning, etc.); and individuals engage in these 

post-application activities for a high-end amount of time every day (represented by data 

reflecting time spent gardening based on survey data).

Given the conservatisms discussed above and the potential compounding nature of these 

conservatisms, EPA is able to rely upon the calculated exposure estimates with confidence that 

exposure is not being underestimated. Cyproconazole’s largest MOE for post-application 

exposure is 520 (>5 times the LOC of 100), which exceeds the waiver criteria. As a result, a 

chemical-specific DFR data are not required.

Conclusions: There is sufficient information available to assess occupational handler and postapplication exposures. Updated occupational handler and post-application exposure assessments 

will be conducted during Registration Review for cyproconazole use on corn, cereals, and 

soybeans. No risk assessments are required for the AD composite wood preservative use. Based 

on existing and anticipated occupational post-application risk estimates and the current 

toxicological PODs, DFR studies are not anticipated to be needed at this time. 

8.0 Public Health and Pesticide Epidemiology 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 cyproconazole. The purpose of the 

database search is to identify potential patterns in the frequency and severity of the health effects 

attributed to cyproconazole exposure. Cyproconazole is not included in the Agricultural Health 
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Study (AHS), and therefore this study does not provide information for this report.

OPP’s IDS includes reports of alleged human health incidents from various sources, including 

mandatory Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) Section 6(a)(2) reports 

from registrants, other federal and state health and environmental agencies, and individual 

consumers. Since 1992, OPP has compiled these reports in IDS. IDS contains reports from 

across the U.S. and most incidents have all relevant product information recorded. Reports 

submitted to the IDS represent anecdotal reports or allegations only, unless otherwise stated in 

the report. 

IDS records incidents in one of two modules: Main IDS and Aggregate IDS:

 

o Main IDS contains incidents resulting in higher severity outcomes and provides 

more detail with regard to case specifics. This system stores incident data for 

death, major and moderate incidents, and it includes information about the 

location, date, and nature of the incident. Main IDS incidents involving only one 

active ingredient (as opposed to pesticide products with multiple active 

ingredients) are considered to provide more certain information about the 

potential effects of exposure from the pesticide. 

o Aggregate IDS contains incidents resulting in less severe human incidents (minor, 

unknown, or no effects outcomes). These are reported by registrants only as 

counts in what are aggregate summaries. 

For the Main IDS, from January 1, 2010 to May 27, 2015, there were no incidents reported 

involving cyproconazole. 

 

In Aggregate IDS, from January 1, 2010 to May 27, 2015, there were two incidents reported 

involving cyproconazole. One incident was classified as minor severity and the other was 

classified as having no or unknown effects. Overall, there are few incidents reported to IDS 

involving cyproconazole. 

The SENSOR-Pesticides database covers 12 states from 1998-2011, although reporting varies 

from state to state. Cases of pesticide-related illnesses are ascertained from a variety of sources, 

including: reports from local Poison Control Centers, state Department of Labor workers’ 

compensation claims when reported by physicians, reports from State Departments of 

Agriculture, and physician reports to state Departments of Health. Although both occupational 

and non-occupational incidents are included in the database, SENSOR-Pesticides focuses on 

occupational pesticide incidents, and is of particular value in providing that information. The 

state coordinator at each of the 12 respective state Departments of Health conducts case followup activities such as obtaining medical records to verify symptoms and severity. Using 

standardized protocol and case definitions derived from poison center reporting, the state 

SENSOR-Pesticide coordinator enters the incident information into the state-based system which 

is sent to NIOSH annually to be aggregated. 

A query of SENSOR-Pesticides 1998-2011 identifies three cases involving cyproconazole. All 

three cases involved multiple active ingredients. All three cases were low in severity.

The AHS is a high-quality, prospective epidemiology study evaluating the link between pesticide 

use and various health outcomes including cancer. The AHS includes private and commercial 
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pesticide applicators and their spouses. If there are AHS findings relevant to a particular 

pesticide going through registration review, the Agency will ensure they are considered in the 

problem formulation/scoping phase of the process and, if appropriate, fully reviewed in the risk 

assessment phase of the process. The AHS includes information on use of 80 different pesticide 

active ingredients commonly used in agriculture. Cyproconazole is not included in the AHS, and 

therefore this study does not provide information for this report.

Conclusions: Based on the low frequency and severity of incident cases reported for 

cyproconazole 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.

9.0 Tolerance Assessment and International Harmonization

U.S. permanent tolerances (listed in 40 CFR §180.485) are summarized in Attachment 5. Codex 

maximum residue limits (MRLs) are established for residues of cyproconazole per se in/on 

numerous commodities. The U.S. tolerance expressions in 40 CFR §180.485(a)(2) and 

§180.485(a)(3) include an additional metabolite than the Codex MRL expression. The numerical 

values are harmonized for all commodities except for field corn stover, soybean seed, wheat 

grain, wheat straw and livestock commodities; for which U.S. tolerance values are lower than the 

corresponding MRLs. There are currently no established Canadian MRLs. Harmonization of 

U.S. tolerances and Codex MRLs will be considered during Registration Review. 

10.0 Environmental Justice

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

most recent cyproconazole human health risk assessment, in accordance with U.S. Executive 

Order 12898, “Federal Actions to Address Environmental Justice in Minority Populations and 

Low-Income Populationsa.” The 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 

highest exposures indicate potential risks of concern, OPP further refines the risk assessments to 

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

11.0 Cumulative

Cyproconazole 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 

 

a http://www.archives.gov/federal-register/executive-orders/pdf/12898.pdf
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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.

12.0 Human Studies

Past cyproconazole risk assessments rely in part on data from studies in which adult human

subjects were intentionally exposed to a pesticide to determine their dermal and inhalation 

exposure. Many such studies, involving exposure to many different pesticides, comprise generic 

pesticide exposure databases such as the Pesticide Handlers Exposure Database (PHED), the 

Outdoor Residential Exposure Task Force (ORETF) Database, the Agricultural Handler 

Exposure Task Force (AHETF), the Antimicrobial Exposure Assessment Task Force (AEATF),

and the ARTF Database. EPA has reviewed all the studies supporting these multi-pesticide 

generic exposure databases, and has found no clear and convincing evidence that the conduct of 

any of them was either fundamentally unethical or significantly deficient relative to the ethical 

standards prevailing at the time the research was conducted. All applicable requirements of 

EPA’s Rule for the Protection of Human Subjects of Research (40 CFR Part 26) have been 

satisfied, and there is no regulatory barrier to continued reliance on these studies.

13.0 Risk Assessment Updates, Data Deficiencies, and Label Revisions

No data deficiencies were identified for cyproconazole. EPA notes the following assessment 

updates will need to be completed during Registration Review:

o Toxicology: 

o Re-evaluation of PODs and UF/SFs.

o Residue Chemistry/Dietary Exposure: 

o A revised dietary-exposure analysis may be required to reflect the most recent 

dietary-exposure models, potentially revised EDWCs (specifically, use of PRZMGW), and/or revised toxicological PODs.

o Occupational/Residential Exposure: 

o Revised occupational handler and post-application risk assessments for the 

conventional uses of cyproconazole will be necessary to reflect the most recent 

HED policies and/or toxicological PODs and UF/SFs. 

o Spray drift and bystander assessments may be necessary to reflect current HED 

policies.

o Aggregate Exposure: 

o Revised aggregate exposure analyses may be required to reflect revised dietary 

exposure estimates and/or changes to the toxicological PODs and UF/SFs.
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14.0 References

Memoranda Relevant to Registration Review.

Author Barcode Date Title

G. Kramer D217295 13-JUN-1996 PP# 5F04537. Cyproconazole in/on Peanuts, Wheat, Beef 

Liver and Imported Bananas. Evaluation of Residue Data 

and Analytical Methods.

G. Kramer D235159 09-JUL-1997 Tolerance Petition for Residues of Cyproconazole in/on 

Imported Coffee.

G. Kramer D330713 16-NOV-2007 PP# 6F7072. Cyproconazole. Petition for Tolerances on 

Soybeans, Wheat, and Corn. Summary of Analytical 

Chemistry and Residue Data. 

M. Rust-Clock 

et al.

D330274 16-NOV-2007 Petition No: 6F7072. Cyproconazole: Human-Health Risk 

Assessment for Proposed Uses on Corn, Soybean and Wheat.

G. Kramer D349906 27-FEB-2008 PP# 6F7072. Cyproconazole. Petition for Tolerances on 

Soybeans, Wheat, and Corn. Revised Summary of 

Analytical Chemistry and Residue Data.

M. Rust-Clock 

et al.

D349841 27-FEB-2008 Petition No: 6F7072. Cyproconazole: Revised HumanHealth Risk Assessment for Proposed Uses on Corn, 

Soybean and Wheat.

M. Sahafeyan D349907 28-FEB-2008 PP# 6F7072. Cyproconazole. Revised Tier I Acute and 

Chronic Aggregate Dietary (Food and Drinking Water) 

Exposure and Risk Assessments for the Section 3 

Registration Action on Soybean, Wheat, and Corn.

M. Rust-Clock 

et al.

D352237 02-MAY-2008 Cyproconazole. Updated Revised Human-Health Risk 

Assessment for Proposed Uses on Corn, Soybean and Wheat.

S. Levy et al. D399957 03-OCT-2012 Cyproconazole. Tolerance Petition for Residues in/on 

Peanuts. Human-Health Risk Assessment. 

S. Levy D400183 03-OCT-2012 Cyproconazole. Acute and Chronic Aggregate Dietary 

(Food + Drinking Water) Exposure and Risk Assessment for 

the Section 3 Registration Action Use on Peanuts.

G. Kramer D400182 03-OCT-2012 Cyproconazole. Proposed New Use on Peanuts. Summary 

of Analytical Chemistry and Residue Data.

G. Kramer D391959 29-AUG-2012 Cyproconazole. Petition for Tolerances on Soybeans, 

Wheat, and Corn. Response to Health Effects Division 

(HED) Review of 27-FEB-2008 (DP# 349906).

T. Morton D426493 09-APR-2015 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.

G. Kramer D408524 21-JUL-2015 Cyproconazole. Petition for Tolerances on Soybeans, 

Wheat, and Corn. Submission of Final Report on Field 

Accumulation in Rotational Crops.

S. Recore D429119 15-SEP-2015 Cyproconazole: Tier I (Scoping) Review of Human Incidents 

and Epidemiology

T. Dole D428952 09-SEP-2015 Risk Assessment of New use of Cyproconazole for the 

Protection of Engineered and Composite Wood Products
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Attachments: 

Attachment 1: Chemical Identity Table.

Attachment 2: Cyproconazole Endpoint Selection Tables.

Attachment 3: Cyproconazole Acute, Subchronic, and Chronic Toxicity Profile.

Attachment 4: Summary of Registered Uses.

Attachment 5: Cyproconazole International Residue Limit Status Sheet.

cc: G. Kramer (RAB1)

RDI: RAB1 (9/16/15), J. Rowland (10/7/15), J. Dawson (10/7/15)

G.F. Kramer:S10957:PY-S:(703)305-5079:7509P:RAB1
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Attachment 1: Chemical Identity Table.

Table A1.1. Cyproconazole Nomenclature.

Chemical structure

Common name Cyproconazole

Company experimental name SAN619

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

CAS name α-(4-chlorophenyl)-α-(1-cyclopropylethyl)-1H-1,2,4-triazole-1-ethanol

CAS registry number 94361-06-5

End-use products (EP) 0.83 lb ai/gal SC/L (Alto® 100SL Fungicide; EPA Reg. No. 100-1226)

Chemical structure

Common name M14

Company experimental name NOA 421153

Chemical name 2-(4-chlorophenyl)-3-cyclopropyl-1-[1,2,4]triazol-1-yl-butane-2,3-diol

CAS registry number NA

Chemical structure

Common name M36

Company experimental name NOA 405872

Chemical name δ-(4-chlorophenyl)-β,δ-dihydroxy-γ-methyl-1H-1,2,4-triazole-1-hexenoic acid

CAS registry number NA

Compound

Common name (Abbr) Triazole (T)

Chemical Name 1H-1,2,4-triazole

CAS registry number 288-88-0

Compound

Common name (Abbr) Triazole alanine (TA)

Chemical Name α-amino-1H-1,2,4-triazole-1-proanoic acid

N

N

Cl

OH

H C3

N

N

N

Cl

OH

H3C

N

OH

N

N

Cl

OH

N

CH3

O

HO

HO

NH

N

N

N

N

N

NH2

OH

O
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Table A1.1. Cyproconazole Nomenclature.

CAS registry number 114419-45-3

Compound

Common name (Abbr) Triazole acetic acid (TAA)

Chemical Name 1H-1,2,4-triazole-1-acetic acid

CAS registry number 28711-29-7

Table A1.2. Physicochemical Properties of Cyproconazole.

Parameter Value Reference

Melting range 99-106°C D179678, R. Lascola, 9/24/91

pH at 22oC 6.7 ± 0.2

Bulk Density at 20oC 0.5 ± 0.1 g/mL

Water solubility at 25oC 108 mg/L at pH 4.1

93 mg/L at pH 7

109 mg/L at pH 10

MRID 46840803

Solvent solubility

(g/100 mL at 25°C)

n-Hexane 0.2

Diisopropyl ether 2.2

Toluene 10.9

Xylene 11.2

Acetone >20

D179678, R. Lascola, 9/24/91

Vapor pressure at 25oC 2.6 x 10-5 Pa MRID 46840803

Dissociation constant, pKa Compound does not dissociate D179678, R. Lascola, 9/24/91

Octanol/water partition coefficient, 

Log(KOW)

2.91 ± 0.12

UV/visible absorption spectrum Not reported

N

N

N

OH

O
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Attachment 2: Cyproconazole Endpoint Selection Tables (from 2012 Risk Assessment).

Table A2.1. Summary of Toxicological Doses and Endpoints for Cyproconazole for Use in Dietary and 

Non-occupational Human Health Risk Assessments.

Exposure Scenario POD Uncertainty/ 

FQPA SF

RfD, PAD, 

LOC for Risk 

Assessment

Study and Toxicological Effects

Acute Dietary 

(General 

population, 

including infants 

and children)

N/A N/A N/A A dose and endpoint attributable 

to a single dose were not 

identified in the database 

including the developmental 

toxicity studies.

Acute Dietary 

(Females 13-49 

years of age)

NOAEL = 2

mg/kg/day 

UFA = 10X

UFH = 10X

FQPA SF = 1X

aPAD = aRfD

= 0.02

mg/kg/day

Prenatal Developmental toxicity 

Study – New Zealand white 

rabbits.

Developmental LOAEL = 10

mg/kg/day based on increased 

incidence of malformed fetuses 

and litters with malformed 

fetuses.

Chronic Dietary 

(All populations)

NOAEL = 

1.0 

mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 1X

cPAD = cRfD 

= 0.01 

mg/kg/day

Chronic oral toxicity study -

dog.

LOAEL = 3.2 mg/kg/day based 

on liver effects (P450 induction in 

females and histopathology, 

laminar eosinophilic 

intrahepatocytic bodies in males).

Short (1-30 days)-

and Intermediate 

(1-6 months)-

Term Incidental 

Oral

NOAEL = 

1.5

mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 1X

Residential 

LOC for MOE 

= 100

90-day oral toxicity – rat.

LOAEL = 27.3 mg/kg/day based 

on decreased body-weight gain in 

males and increased liver weight 

in females.

Short (1-30 days)-

and Intermediate 

(1-6 months)-

Term Dermal

NOAEL = 10

mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 1X

Residential 

LOC for MOE 

= 100

28-Day Dermal Study – rat.

LOAEL = 100 mg/kg/day, based 

on increased plasma globulin, 

protein and cholesterol, and 

hemosiderin deposition in the 

spleen in females, and 

hypertrophy of the thyroid 

follicular epithelium in both males 

and females.

Short (1-30 days)-

and Intermediate 

(1- 6 months)-Term

Inhalation

NOAEL = 2

mg/kg/day 

(inhalationabsorption 

rate = 100% 

oral 

equivalent)

UFA = 10X

UFH = 10X 

FQPA SF = 1X

Residential 

LOC for MOE 

= 100

Prenatal Developmental toxicity 

Study – New Zealand white 

rabbits.

Developmental LOAEL = 10

mg/kg/day based on increased 

incidence of malformed fetuses 

and litters with malformed 

fetuses.

Cancer (oral, 

dermal, inhalation)

HED classified cyproconazole as “not likely to be carcinogenic to humans” according to 

EPA Proposed Guidelines for Carcinogen Risk Assessment (10-APR-1996).

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). FQPA SF = FQPA Safety Factor. PAD = 

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

of concern. A = 11% dermal absorption-factor from dermal-penetration study (43173701). N/A = not applicable.
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Table A2.2. Summary of Toxicological Doses and Endpoints for Cyproconazole for Use in Occupational 

Human Health Risk Assessments.

Exposure Scenario POD Uncertainty/ 

FQPA SF

RfD, PAD, 

LOC for Risk 

Assessment

Study and Toxicological Effects

Short (1-30 days)-

and Intermediate 

(1-6 months)-

Term Dermal

NOAEL = 10

mg/kg/day

UFA = 10X

UFH = 10X

Occupational 

LOC for MOE 

= 100

28-Day Dermal Study – rats.

LOAEL = 100 mg/kg/day, based 

on increased plasma globulin, 

protein and cholesterol, and 

hemosiderin deposition in the 

spleen in females, and 

hypertrophy of the thyroid 

follicular epithelium in both males 

and females.

Short (1-30 days)-

and Intermediate 

(1- 6 months)-Term

Inhalation

NOAEL = 2

mg/kg/day 

(inhalationabsorption 

rate = 100% 

oral 

equivalent)

UFA = 10X

UFH = 10X

Occupational 

LOC for MOE 

= 100

Prenatal Developmental toxicity 

Study – New Zealand white 

rabbits.

Developmental LOAEL = 10

mg/kg/day based on increased 

incidence of malformed fetuses 

and litters with malformed 

fetuses.

Cancer (oral, 

dermal, inhalation)

HED classified cyproconazole as “not likely to be carcinogenic to humans” according to 

EPA Proposed Guidelines for Carcinogen Risk Assessment (10-APR-1996).

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). FQPA SF = FQPA Safety Factor. MOE = 

margin of exposure. LOC = level of concern. A = 11% dermal absorption-factor from dermal-penetration study 

(43173701). 
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Attachment 3: Cyproconazole Acute, Subchronic, and Chronic Toxicity Profile.

Table A3.1. Acute Toxicity of Cyproconazole.

Guideline No. Study Type Results Toxicity 

Category

870.1100 

(81-1) Acute Oral (rat) M: 1020 mg/kgF: 1330 mg/kg III

870.1100 

(81-1) M-36 metabolite, Acute Oral (rat) MRID-43674701, >2000 mg/kg III

870.1100 

(81-1) M-36 metabolite, Acute Oral (mouse) MRID-43674732 >2000 mg/kg III

870.1200 

(81-2) Acute Dermal (rabbit) LD50 >2000 mg/kg III

870.1300 

(81-3) Acute Inhalation (rat) LC50 >5.6 mg/L III

870.2400 

(81-4) Primary Eye Irritation (rabbit) Not an eye irritant IV

870.2500 

(81-5 ) Primary Skin Irritation (rabbit) Not a dermal irritant IV

87.2600 

(81-6) Dermal Sensitization (guinea pig) Not a dermal sensitizer N/A

Table A3.2. Subchronic, Chronic, and Other Toxicity Profile of Cyproconazole.

Guideline 

No. Study Type MRID No. (year)/ Classification /Doses Results

870.3050 28-Day oral (rat) 40624305 (1986)

Acceptable/nonguideline 

0, 10, 30,100, 300, and 

1000 ppm 

0, 0.5, 1.5, 5.0, 15, 50 

mg/kg/day

NOAEL= 5 mg/kg/day.

LOAEL = 15 mg/kg/day, based on elevated LDH, 

increased liver weight (relative and absolute) and 

liver vacuolization.

870.3100 90-Day oral 

toxicity (rat)

40607718 (1986)

Acceptable/nonguideline

0, 20, 80, or 320 ppm

0, 1, 4, and 16 mg/kg/day

NOAEL = 20 ppm (1 mg/kg/day).

LOAEL = 80 ppm (4 mg/kg/day) based on 

increased incidences of centrilobular hepatocyte 

hypertrophy. 

870.3100 90-Day oral 

toxicity (rat)

43078601 (1993)

Acceptable/

supplementary 

0, 20, 350, 700, or 1400 

ppm

M/F: 0/0, 1.5/2.0, 

27.3/35.4, 55.8/74.3, and

114.5/139.4 mg/kg/day

NOAEL = 20 ppm (1.5/2.0 mg/kg/day in 

males/females).

LOAEL = 350 ppm (27.3/35.4 mg/kg/day in 

males/females), based on decreased body-weight 

gain in males and increased liver weights in 

females.
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Table A3.2. Subchronic, Chronic, and Other Toxicity Profile of Cyproconazole.

Guideline 

No. Study Type MRID No. (year)/ Classification /Doses Results

870.3100 90-Day oral 

toxicity (rat)

46152901 (1999)

Acceptable/guideline 

0, 20, 350, 700, or 1400 

ppm (equivalent to 0/0, 

1.4/1.6, 24.7/29.6, 

52.8/57.3, and 

106.8/118.1 mg/kg/day 

in males/females)

NOAEL = 20 ppm (equivalent to 1.4/1.6 

mg/kg/day in males/females).

LOAEL = 350 ppm (equivalent to 24.7/29.6 

mg/kg/day in males/females), based on increased 

liver weight and increased incidence of liver 

hypertrophy in both sexes and increased 

incidence of liver fatty change in males.

870.3100 90-Day oral 

toxicity (mouse)

46950013 (1987)

Acceptable/nonguideline 

0, 5, 15, 300, or 600 ppm 

M: 0, 0.7, 2.2, 43.8, or 

88.7 mg/kg bw/d 

F: 0, 1.0, 3.2, 70.2, or 

128.2 mg/kg bw/day 

NOAEL = 15 ppm (2.2 and 3.2 mg/kg bw/day in 

males and females).

LOAEL = 300 ppm (43.8 and 70.2 mg/kg bw/day 

in males and females), based on decreased bodyweight gain in both sexes and evidence of liver 

effects (increased liver weight in both sexes, 

periacinar hepatocytic eosinophilia in males, and 

single-cell hepatocyte necrosis in both sexes). 

870.3150 90-Day oral 

toxicity (dog)

40607719 (1985)

Acceptable/guideline 

0, 20, 100, 500 ppm

0, 0.8, 4.0, and 20.0 

mg/kg/day

NOAEL = 4.0 mg/kg/day.

LOAEL = 20.0 mg/kg/day, based on slack muscle 

tone, inhibited body weight gain, liver effects

(increased alkaline phosphatase and gamma 

glutamyl transferase) and histopathological 

evidences (hepatocytomegaly, degeneration of 

single hepatocytes and cytoplasmic inclusions).

870.3200 21-Day dermal 

toxicity (rat)

40624306 (1988)

Acceptable/guideline 

0, 50, 250, 1250 

mg/kg/day 

NOAEL = 250 mg/kg/day.

LOAEL = 1250 mg/kg/day, based on decreased 

body-weight gain and food consumption (M), 

increased AST (males), creatinine (females), and 

cholesterol (both sexes).

870.3200 28-Day dermal 

toxicity (rat)

48840824 (2000)

Acceptable/guideline 

0, 10, 100, 1000 

mg/kg/day

NOAEL = 10 mg/kg bw/day. 

LOAEL = 100 mg/kg bw/day, based on increased 

plasma globulin, protein and cholesterol, and 

hemosiderin deposition in the spleen in females, 

and hypertrophy of the thyroid follicular 

epithelium in both males and females.

870.3700a Prenatal 

developmental in 

(rat)

40607721 (1985)

Acceptable/guideline

0, 6, 12, 24, 48 

mg/kg/day

Maternal NOAEL = 6 mg/kg/day.

Maternal LOAEL = 12 mg/kg/day, based on 

decreased body-weight gain during dosing.

Developmental NOAEL = 6 mg/kg/day.

Developmental LOAEL = 12 mg/kg/day, based 

on increased incidence of supernumerary ribs, 

malformations (hydrocephaly) at 24 & 48 

mg/kg/day and cleft palate at 48 mg/kg/day.

870.3700b Prenatal 

developmental in 

(chinchilla rabbit)

40607720 (1986)

Unacceptable/guideline

0, 2, 10, 50 mg/kg/day

Maternal NOAEL = 10 mg/kg/day.

Maternal LOAEL = 50 mg/kg/day, based on 

inhibited body-weight gain during treatment.

Developmental NOAEL <2 mg/kg/day.

Developmental LOAEL = 2 mg/kg/day, based on 

incidence of hydrocephalus internus.

870.3700b Prenatal 

developmental in 

(New Zealand 

White rabbit)

42175401 (1991),

Acceptable/guideline

0, 2, 10, 50 mg/kg/day

Maternal NOAEL = 10 mg/kg/day.

Maternal LOAEL = 50 mg/kg/day, based on 

decreased body-weight gain.

Developmental NOAEL = 2 mg/kg/day.

Developmental LOAEL = 10 mg/kg/day, based 

on increased incidence of malformed fetuses and 

litters with malformed fetuses.
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Table A3.2. Subchronic, Chronic, and Other Toxicity Profile of Cyproconazole.

Guideline 

No. Study Type MRID No. (year)/ Classification /Doses Results

870.3800 Reproduction and 

fertility effects

(rat)

40607723 (1987)

Acceptable/guideline

0, 4, 20, 120 ppm 

0, 0.28/0.33, 1.39/1.67, 

or 8.29/9.88 mg/kg/d

Parental NOAEL = 20 ppm (1.39 mg/kg/day).

Parental LOAEL = 120 ppm (8.29 mg/kg/day), 

based on liver effects (increased lipid storage and 

relative weight in males and increased relative 

weight in females).

Reproductive NOAEL = 120 ppm (8.29 

mg/kg/day), although gestation length was 

slightly increased and litter sizes were decreased, 

the changes are not considered treatment-related.

Reproductive LOAEL was not determined.

Offspring NOAEL = 120 ppm (8.29 mg/kg/day). 

Offspring LOAEL was not determined.

870.4100b Chronic toxicity

(dog)

41212901 (1988)

Acceptable/guideline

0, 30, 100, and 350 ppm 

M/F: 0/0, 1.0/1.0, 

3.2/3.2, and 12.1/12.6 

mg/kg/d)

NOAEL = 30 ppm (1.0 mg/kg/day).

LOAEL = 100 ppm (3.2 mg/kg/day), based on 

liver effects (P450 induction in females and 

histopathology, laminar eosinophilic 

intrahepatocytic bodies in males).

870.4200b Carcinogenicity 

(mouse)

41147201(1989)

Acceptable/guideline

0, 5, 15, 100,200 ppm 

M/F: 0/0.69/1.03, 

1.84/2.56, 13.17/17.65, 

or 27.85/36.30 mg/kg/d

NOAEL = M/F: 1.8/2.6 mg/kg/day.

LOAEL = M/F: 13.2/17.7 mg/kg/day, based on 

increased incidence of hepatocytic single-cell 

necrosis; increased incidence of hepatocellular 

adenomas and carcinomas.

870.4300 Combined Chronic

Toxicity/Carcinoge

nicity (rat)

41164701 (1988)

Acceptable/guideline

0, 20, 50, or 350 ppm

M/F: 0/0, 1.0/1.2, 

2.2/2/7 and 15.6/21.8 

mg/kg/d 

NOAEL = 50 ppm (2.2 mg/kg/day).

LOAEL = 350 ppm (15.6 mg/kg/day), based on 

decreased body weight and increased incidence of 

fatty infiltration in liver (M). Dosing was 

inadequate in females.

870.5100 Bacterial Reverse

Mutation Test

40607725 (1986)

Acceptable/guideline

0, 1, 5, 10, 100, 500, 

1000 ug/plate w/wt rat 

S9 mix.

Negative.

870.5100 Bacterial Reverse

Mutation Test

40624307 (1985)

Unacceptable/guideline

0, 10, 100, 250, 400, 

500, or 550 ug/plate 

w/wt rat S9 mix.

Negative.

870.5300 In Vitro Gene 

Mutation assay in 

Chinese Hamster 

Ovary cells

40607726 (1985)

Acceptable/guideline

0, 20, 50, 100, or 200 

ug/mL w/wt S9.

Negative.

870.5375 In Vitro 

Mammalian 

Chromosomal 

Aberration

41757801 (1990)

Unacceptable/guideline

60.1, 100.0, 150.0, or 

200 ug/mL wt S9; 45.0, 

59.9, 99.9, or 150.0 with 

S9.

Cannot be interpreted.
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Table A3.2. Subchronic, Chronic, and Other Toxicity Profile of Cyproconazole.

Guideline 

No. Study Type MRID No. (year)/ Classification /Doses Results

870.5375 In Vitro 

Mammalian 

Chromosomal 

Aberration

46950019 (1995)

Acceptable/guideline

0, 50, 100, 200, or 400 

μg/mL without S9.

0, 25, 50, 100, or 200 

μg/mL with metabolic 

activation.

0, 50, 100, 200, or 400 

μg/mL without S9.

0, 100, 200, 400, or 800 

μg/mL with metabolic 

activation.

Negative.

870.5375 In Vitro 

Mammalian 

Chromosomal 

Aberration

41757701 (1988)

Unacceptable/guideline

100, 150 or 200 ug/mL 

wt S9; 100, 150, 200, or 

250 with S9.

Positive w/wt S9. 

870.5395 In Vivo

Mammalian 

Cytogenetics -

Erythrocyte 

Micronucleus 

Assay in Mice

40607728 (1984)

Acceptable/guideline

0, 16.7, 55.7, 167 mg/kg

Negative.

Cell 

Transformation

40607724 (1985)

Acceptable

0, 20, 50, 100, or 200 

ug/mL w/wt S9 

(assumed)

Negative.

870.5450 Rodent Dominant 

Lethal

41961401 (1991)

Acceptable/guideline

20, 40, or 80 mg/kg/d

Negative.

870.5550 Unscheduled DNA

Synthesis in 

Mammalian

Cells in Culture

40607729 (1988)

Unacceptable/guideline

0.15,0.5, 1.5, 5, 15, 50, 

100, 150 ug/mL 

Cannot be evaluated.

870.5550 Unscheduled DNA

Synthesis in 

Mammalian

Cells in Culture

40607727 (1985)

Unacceptable/guideline

0.15,0.5, 1.5, 5, 15, 50, 

100, 150 ug/mL 

Cannot be evaluated.

870.7485 Metabolism and 

pharmacokinetics

(rat)

41701901 (1987)

Acceptable/guideline

oral - 10 mg/kg , 910 

mg/kg x 14 days;

iv - 10 and 130 mg/kg

Absorption, distribution, excretion, and blood 

kinetics were examined. Almost completely 

absorbed in males (84%) and females (106%), 

extensively metabolized; diastereomers A & B of 

parent + 13 metabolites identified & isolated; 35 

metabolites detected; metabolic profiles for urine, 

feces, bile similar; major metabolic reactions 

include oxidative elimination of triazole ring; 

hydroxylation of C bearing CH3 group; oxidation 

of CH3 group to carbinol & further to oxidation 

carboxylic acid; rapid excretion with majority 

appearing in feces (biliary excretion); residual 14C 

found within renal fat, adrenals, liver; potential 

liver accumulation in long-term studies.
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Table A3.2. Subchronic, Chronic, and Other Toxicity Profile of Cyproconazole.

Guideline 

No. Study Type MRID No. (year)/ Classification /Doses Results

870.7485 Metabolism and 

pharmacokinetics

(rat)

46152903 (2003)

0.5 mg/kg. Animals 

were dosed with the 

radioactive test substance 

daily for up to 14 days.

The majority of the total administered dose 

(96.5%) was recovered in the feces (56.3%) and 

urine (40.2%). The highest blood levels were 

found ten days after the start of dosing (0.08-ppm 

cyproconazole equivalents). Three days after the 

final dosing, radioactivity was almost completely 

excreted. The calculated half-life for the 

depletion of radioactivity (assuming mono-phasic 

first-order kinetics) from the tissues ranged from 

one to three days. The greater persistence and 

longer half-life of radioactivity in blood 

compared to plasma indicated some partitioning 

of radioactivity into the red blood cells. The 

highest concentrations of radioactivity were 

observed in the liver (1.37-ppm cyproconazole 

equivalents), adrenals (0.93 ppm), lungs (0.56 

ppm), fat (0.49 ppm), kidneys (0.25 ppm), 

pancreas, (0.22 ppm), and ovaries (0.16 ppm) 

seven days after the start of dosing. Urine was 

found to contain at least 21 metabolite fractions 

by two-dimensional thin-layer chromatography 

(TLC). Individual fractions were detected in 

similar proportions on Days 0-1, 6-7, and 13-14. 

The combined urinary metabolite fractions 

accounted for 20.8-41.0% of the dailyadministered doses.

870.7600 Dermal penetration 

(rat)

43 173701 (1993),

Acceptable/guideline

0, 2.5, 15, and 120 

ug/cm2for 0.5, 1, 2, 4, 

10, and 24 hr.

At dose levels of 2.5, 15, and 120 μg ai/cm2 

cyproconazole, the percent absorbed (0.87-7.69, 

0.59-11.88, and 0.92-0.89, respectively) increased 

with duration of exposure and decreased with 

dose. The quantity absorbed increased with dose 

and duration of exposure. At the 10-hour 

exposure time point, 10.8 1% of the low dose was 

absorbed. % absorbed = 11% for 10 hours
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Attachment 4: Summary of Registered Uses.

Table A4.1. Summary of Cyproconazole Application Scenarios.

App. Timing; 

Type; and 

Equip.

Formulation (EPA Reg. 

No.)

App. Rate

fl oz/A

Max. #. App. 

per Season

Max. Seasonal App. 

Rate (lb ai/acre) Use Directions and Limitations

Soybeans

Foliar

Broadcast 

application

Groundboom, 

chemigation, 

aerial

Alto 100SL® SC

0.83 lb ai/gal

EPA Reg. No. 100-1226

2.75 – 5.5 

Not specified

11 fl oz/A/season

0.072 lb ai/A/year

 REI = 12 hours

 PHI = 30 days

 PGI = 14 days

 Do not use soybean forage or hay as 

livestock feed if making for than one 

application at 6.8 fl oz product/A 

(0.036 lb ai/A/year).

AzureTM Xtra SC

0.67 lb ai/gal

EPA Reg. No. 228-728;

Quadris Xtra® SC

0.67 lb ai/gal

EPA Reg. No. 100-1225

4.0 – 6.8 

13.6 fl oz/season

0.072 lb ai/A/year

Aproach® Prima SC 

0.67 lb ai/gal

EPA Reg. No. 352-883

5.0 – 6.8 2

Peanuts

Foliar

Broadcast 

application

Groundboom, 

chemigation, 

aerial

Alto 100SL® SC

0.83 lb ai/gal

EPA Reg. No. 100-1226

5.5 2

11.0 fl oz/A/season

0.072 lb ai/acre/year

 REI = 12 hrs

 PHI = 30 days

Cereals - Wheat & Triticale

Foliar

Broadcast 

application

Groundboom, 

chemigation, 

aerial

Alto 100SL® SC

0.83 lb ai/gal

EPA Reg. No. 100-1226

1.5 – 5.5 

not specified

5.5 fl oz/A/season

0.036 lb ai/A/season

 REI = 12 hrs

 PHI wheat = 30 days

 PHI forage or hay = 21 days

AzureTM Xtra SC

0.67 lb ai/gal

EPA Reg. No. 228-728;

Quadris Xtra® SC

0.67 lb ai/gal

EPA Reg. No. 100-1225

3.5 – 6.8 

6.8 fl oz/A/season

0.036 lb ai/A/season

Aproach® Prima SC

0.67 lb ai/gal

EPA Reg. No. 352-883

3.4 – 6.8 2

 REI = 12 hours

 PHI grain = 45 days

 PHI forage or hay = 21 days

Corn - field & seed

Foliar

Broadcast 

application

Groundboom, 

chemigation, 

aircraft 

Alto 100SL® SC

0.83 lb ai/gal

EPA Reg. No. 100-1226

2.75 – 5.5

2

5.5 fl oz/A/season

0.036 lb ai/A/season

 REI = 12 hrs

 PHI grain or ear = 30 days

 PHI silage = 21 days

Quadris Xtra® SC

0.67 lb ai/gal;

EPA Reg. No. 100-1225;

Aproach® Prima SC

0.67 lb ai/gal

EPA Reg. No. 352-883;

AzureTM Xtra SC

0.67 lb ai/gal

EPA Reg. No. 228-728

3.5 – 6.8

6.8 fl oz/A/season

0.036 lb ai/A/season

Abbreviations: REI = restricted-entry interval, PHI = postharvest interval, PGI = pre-grazing interval.
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Attachment 5: Cyproconazole International Residue Limit Status Sheet.

International Residue Limits 

Cyproconazole (128993; Date of Request: 08/31/2015)

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico2 Codex3

40 CFR §180.485 (a) General. (1) 

Compliance with the proposed 

tolerance levels specified below is 

to be determined by measuring 

only cyproconazole (α-(4-

chlorophenyl)-α-(1-

cyclopropylethyl)-1H-1,2,4-

triazole-1-ethanol)

None Cyproconazole

The residue is fat 

soluble.

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

US Canada Mexico2 Codex3

Aspirated grain fractions 2.5

Cattle, fat 0.01

Cattle, meat byproducts (except 

liver) 0.01 0.5 edible offal (mammalian)

Coffee bean, green (Imported)1 0.1 0.07 coffee beans

0.1 coffee beans roasted

Corn, field, forage 0.60

Corn, field, grain 0.01 0.01 (*)

Corn, field, stover 1.2 2 maize fodder (dry)

Goat, fat 0.01

Goat, meat byproducts (except 

liver) 0.01 0.5 edible offal (mammalian)

Horse, fat 0.01

Horse, meat byproducts (except 

liver) 0.01 0.5 edible offal (mammalian)

Peanut 0.01

Peanut, hay 6.0

Sheep, fat 0.01

Sheep, meat byproducts (except 

liver) 0.01 0.5 edible offal (mammalian)

Soybean, forage 1.0

Soybean, hay 3.0 3 soya bean fodder

Soybean, oil 0.10 0.1 soya bean oil, 

refined

Soybean, seed 0.05 0.07 soya bean (dry)

Wheat, forage 0.80

Wheat, grain 0.05

0.08 cereal grains 

(except maize, rice and 

sorghum)

Wheat, grain, milled byproducts 0.10

Wheat, hay 1.3

Wheat, straw 0.90

5 straw and fodder (dry) 

of cereal grains (except 

maize, rice and 

sorghum)

MRLs with No US Equivalent

Beans (dry) 0.02 (*)
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Meat (from mammals other than 

marine mammals)

0.02 (fat)

Peas (dry) 0.02 (*)

Peas, shelled (succulent seeds) 0.01 

Rape seed 0.4

Sugar beet 0.05

Residue Definition:

US Canada Mexico2 Codex3

40 CFR §180.485 (a) General. (2) Compliance 

with the tolerance level specified below is to be 

determined by measuring only the sum of 

cyproconazole (α-(4-chlorophenyl)-α-(1-

cyclopropylethyl)-1H-1,2,4-triazole-1-ethanol) 

and its metabolite δ-(4-chlorophenyl)-β,δdihydroxy-γ-methyl-1H-1,2,4-triazole-1-

hexenoic acid, calculated as the stoichiometric 

equivalent of cyproconazole

Same as above

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

US Canada Mexico2 Codex3

Milk 0.02 0.01

Residue Definition:

US Canada Mexico2 Codex3

40 CFR §180.485 (a) General. (3) Compliance 

with the tolerance level specified below is to be 

determined by measuring only the sum of 

cyproconazole (α-(4-chlorophenyl)-α-(1-

cyclopropylethyl)-1H-1,2,4-triazole-1-ethanol) 

and its metabolite 2-(4-chlorophenyl)-3-

cyclopropyl-1-[1,2,4]triazol-1-yl-butane-2,3-

diol, calculated as the stoichiometric equivalent 

of cyproconazole

Same as above

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

US Canada Mexico2 Codex3

Cattle, liver 0.50 0.5 edible offal 

Goat, liver 0.50 (mammalian)

Hog, liver 0.01

Horse, liver 0.50

Sheep, liver 0.50

MRLs with No US Equivalent

Eggs 0.01 (*)

Poultry meat 0.01 (*)

Poultry, edible offal of 0.01 (*)

Completed: M. Negussie; 09/04/15

1 There are no U.S. registrations as of February 15, 2008 for use on coffee bean.

2 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.

3 * = 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.