Fenbuconazole Human Health Risk Assessment DP No. 0403041 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

Date: January 31, 2013 

OFFICE OF 

CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

{g SUBJECT: Fenbuconazole: Human Health Risk Assessment for an Increased Tolerance for 

Residues in Peppers, and a Label Amendment for the Enable® 2F Product. 

PC Code: 1290 II DP Barcode: 0403041 

Decision No.: 465307, 468478 

Petition No.: 2F8034 

Registration No.: 62719-421; 62719-416 

Risk Assessment Type: Single Chemical Aggregate 

TXRNo.: NA 

Regulatory Action: Section 3; Tolerance Amendment 

Case No.: 7012 

CAS No.: 114360-43-6 

MRIDNo.: NA 40 CFR: 180.480 

FROM: 

;/ (} 

Linnea J. Hansen, Ph.D, Biologist and Risk Assesso ~ t 

Dennis McNeilly, Chemist 8___ IV1 t- 'Y[ 

Risk Assessment Branch II tr' -

Health Effects Division (7509P) 

THROUGH: Christina Swartz, Chief 

Elizabeth Holman, Chemist ~ \~ 

Risk Assessment Branch II 

Health Effects Division (7509P) 

TO: Erin Malone 

Fungicide Branch 

Registration Division (7505P) 

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Fenbuconazole Human Health Risk Assessment DP No. D403041 

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1.0 Executive Summary ........................................................................................................... 4

2.0 HED Recommendations .................................................................................................... 6

2.1 Data Deficiencies ............................................................................................................ 6

2.2 Tolerance Considerations .............................................................................................. 6

2.2.1 Enforcement Analytical Method ............................................................................... 7

2.2.2 Recommended Tolerances ......................................................................................... 7

2.2.3 Revisions to Petitioned-For Tolerances .................................................................... 7

None. ........................................................................................................................................... 7

2.2.4 International Harmonization..................................................................................... 7

2.3 Label Recommendations................................................................................................ 7

3.0 Introduction ........................................................................................................................ 8

3.1 Chemical Identity ........................................................................................................... 8

3.2 Physical/Chemical Characteristics ............................................................................... 9

3.3 Pesticide Use Pattern ...................................................................................................... 9

3.4 Anticipated Exposure Pathways ................................................................................. 10

3.5 Consideration of Environmental Justice .................................................................... 10

4.0 Hazard Characterization and Dose-Response Assessment .......................................... 11

4.1 Summary of Toxicological Effects .............................................................................. 11

4.2 Safety Factor for Infants and Children (FQPA Safety Factor) ............................... 13

4.2.1 Completeness of the Toxicology Database .............................................................. 13

4.2.2 Evidence of Neurotoxicity ........................................................................................ 13

4.2.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal ........ 14

4.2.4 Residual Uncertainty in the Exposure Database ................................................... 14

4.3 Toxicity Endpoint and Point of Departure Selections .............................................. 14

5.0 Dietary Exposure and Risk Assessment ......................................................................... 16

5.1 Residues of Concern Summary and Rationale .......................................................... 16

5.2 Food Residue Profile .................................................................................................... 18

5.3 Water Residue Profile .................................................................................................. 21

5.4 Dietary Risk Assessment .............................................................................................. 22

5.4.1 Description of Residue Data Used in Dietary Assessment .................................... 22

5.4.2 Percent Crop Treated Used in Dietary Assessment .............................................. 23

5.4.3 Acute Dietary Risk Assessment ............................................................................... 23

5.4.4 Chronic Dietary Risk Assessment ........................................................................... 24

5.4.5 Cancer Dietary Risk Assessment............................................................................. 24

5.4.6 Summary Table......................................................................................................... 24

6.0 Residential (Non-Occupational) Exposure/Risk Characterization ............................. 25

6.5 Residential Bystander Post-application Inhalation Exposure ................................. 25

6.6 Spray Drift .................................................................................................................... 25

7.0 Aggregate Exposure/Risk Characterization .................................................................. 26

7.1 Acute & Chronic Aggregate Risk ............................................................................... 26

7.2 Short- and Intermediate-Term Aggregate Risk ........................................................ 26

8.0 Cumulative Exposure/Risk Characterization ............................................................... 26

9.0 Occupational Exposure/Risk Characterization ............................................................ 27

10.0 References ......................................................................................................................... 29

Appendix A. International Residue Limits .............................................................................. 31

Appendix B. Toxicology Profile ................................................................................................ 31
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B.1 Toxicology Data Requirements ................................................................................... 31

B.2 Toxicity Profiles ............................................................................................................ 33

Appendix C. Physical/Chemical Properties ............................................................................. 42

Appendix D. Review of Human Research................................................................................ 43
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1.0 Executive Summary 

A human health risk assessment has been conducted to support a proposed increased tolerance 

for residues of the fungicide fenbuconazole on peppers. Fenbuconazole a broad spectrum 

triazole (conazole) fungicide currently registered for use on the following food/feed crops: 

almonds, apples, bananas, bushberries (subgroup 13-B), citrus fruits (group 10), cranberries, 

pecans, peanuts, peppers, stone fruits (group 12), sugar beets, and wheat. Tolerances are 

established for the combined residues of fenbuconazole and its lactone metabolites, expressed as 

parent, in/on plant commodities at levels ranging from 0.05 ppm in/on almonds and pecans to 40 

ppm in citrus oil [40 CFR §180.480(a)]. Tolerances are also established at 0.05 ppm for the 

combined residues in livestock commodities. 

Dow AgroSciences LLC is proposing to bridge fenbuconazole residue data for peppers from a 

product currently registered for use on peppers to a new product formulation. The tolerance for 

peppers was initially established based on field trial data submitted for the Indar® 75 WSP 

formulation (EPA Reg. No. 62719-421). The registrant then submitted a bridging study to 

translate residue data from Indar® 75 WSP to the proposed new product Enable® 2F (EPA Reg. 

No. 62719-416), a flowable, or suspension concentrate (SC) formulation of fenbuconazole. 

Indar® 75 WSP is a wettable powder formulation packed in water-soluble bags containing 75.0% 

active ingredient (ai), while Enable® 2F is a liquid containing 23.5% ai (2 lb ai/gal). Although 

the use pattern for peppers is the same on the two labels, bridging residue data indicated that an 

increased tolerance for peppers would be needed to support the new formulation. Based on the 

existing residue data and HED’s review of the additional bridging data, a permanent tolerance of 

1.0 on peppers is proposed for the combined residues of fenbuconazole and its lactone 

metabolites, expressed as fenbuconazole. 

The toxicology database for fenbuconazole is largely complete, lacking only an immunotoxicity 

study. Although acute and subchronic neurotoxicity have not been submitted, HED’s Hazard 

Science Policy Council (HASPOC) concluded that these studies are not required, taking into 

consideration the lack of observed neurotoxic effects for fenbuconazole as well as many other 

triazole fungicides. A route-specific rat inhalation study has not been submitted, but is also not 

required based on HED’s determination that fenbuconazole shows no evidence of portal-of-entry 

effects, has low acute inhalation toxicity and very high MOEs for occupational inhalation 

exposure. Since the previous assessment, rabbit developmental toxicity and rat metabolism 

studies were submitted; the findings of these studies are consistent with the existing data and do 

not affect the overall characterization of hazard or selection of doses and endpoints for risk 

assessment. The main target organ of fenbuconazole is the liver. Increased liver weight, 

hepatocellular hypertrophy and clinical chemistry changes were observed in the rat, dog and 

mouse following subchronic and chronic exposure. In the rat, effects on the thyroid were also 

observed. Kidney and adrenal weights were increased in dogs after chronic exposure. 

Fenbuconazole is classified as a “Group C,” or possible human carcinogen, based on an 

increased incidence of liver tumors in male and female mice and thyroid tumors in male rats. A 

cancer potency factor has been used to estimate potential cancer risk associated with 

fenbuconazole uses. 
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The required 10x Food Quality Protection Act (FQPA) Safety Factor was reduced to 1x based on 

both toxicity and exposure considerations: 1) the toxicity database is largely complete, missing 

only the immunotoxicity study; 2) there was no evidence of qualitative or quantitative 

susceptibility in the developmental and reproductive toxicity studies; 3) there was no evidence of 

neurotoxicity, and a developmental neurotoxicity study is not required; 4) there was no evidence 

of immunotoxicity in the existing database; 5) the exposure assessment was based on field trial 

residues and modeled drinking water estimates which will not underestimate dietary exposure 

and risk; and 6) there are no residential uses for the chemical. 

For acute dietary exposure, the dose and endpoint for females age 13-49 were 30 mg/kg/day 

based on increased resorptions and decreased live fetuses per dam at the lowest observed adverse 

effects level (LOAEL) of 75 mg/kg/day. No hazard was identified for acute dietary exposure 

and risk for the general population. For chronic dietary exposure to all populations, the dose and 

endpoint were 3 mg/kg/day based on decreased body weight gain and effects on the thyroid and 

liver at the LOAEL of 30.6 mg/kg/day. Inhalation exposure was assessed based on the no 

observed adverse effects level (NOAEL) of 5.1 mg/kg/day from the rat 90-day oral study, with 

decreased body weight and liver effects observed at the LOAEL of 25.3 mg/kg/day. This 

endpoint has changed since the prior assessment, which was based on effects observed in the rat 

chronic study. No hazard was identified for dermal exposure. 

Adequate studies are available to characterize the metabolism of fenbuconazole in plants and 

animals. Residues of concern in/on plants, including peppers, in rotational crops and in animal 

commodities are the parent fenbuconazole (RH-7592) and its lactone metabolites, RH-9129 and 

RH-9130. For rotational crops other than the primary crop, plantback intervals specified on the 

existing labels and proposed supplemental labeling obviate the need for limited field rotational 

crop trials and associated rotational crop tolerances. 

HED used modeling to assess acute, chronic and cancer aggregate dietary exposure to 

fenbuconazole. For acute dietary exposure, tolerance-level residues and 100% crop treated 

values were used. For chronic and cancer dietary exposure, a somewhat refined analysis using 

average field trial residues, and 100% crop treated values for the non-cancer dietary assessment. 

The cancer analysis is further refined in that it makes use of average percent crop treated 

estimates. Dietary non-cancer exposure and risk estimates are well below HED’s level of 

concern of 100% of the acute and chronic population adjusted doses (aPAD and cPAD, 

respectively). Cancer risk is estimated at 2.2 x 10-6. Actual cancer risk is likely to be much 

lower, since the residue inputs based on field trial data (as opposed to monitoring data) and the 

assumption of upper bound %CT estimates are expected to overestimate dietary exposure and 

risk. 

A non-dietary residential exposure assessment has not been performed because there are no 

registered residential uses of fenbuconazole. Consequently, dietary sources (food plus drinking 

water) are the only sources of exposure to fenbuconazole, and a separate aggregate assessment is 

not required. HED considered the potential for the increased tolerance in peppers to affect the 

Agency’s conclusions regarding aggregate exposure to free triazole and its conjugates. HED 

concluded that the increased tolerance does not have an impact on aggregate exposure to free 

triazole and its conjugates, and the risks are not of concern (D403618, T. Morton, 8/1/12). 
Fenbuconazole Human Health Risk Assessment DP No. D403041 

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HED has determined that new occupational exposure and risk assessments are not needed to 

ensure adequate protection of occupational workers mixing, loading and applying fenbuconazole 

to peppers, based on results of the previous risk assessment for peppers, and considering the 

identical use patterns for the two formulations. Occupational exposure and risk for 

fenbuconazole were previously assessed using baseline personal protective equipment (PPE). A 

quantitative non-cancer dermal exposure and risk assessment was not performed because no 

dermal hazard was identified. All non-cancer risks for inhalation exposure were below HED’s 

level of concern (MOE >100). Combined dermal and inhalation cancer risk for occupational 

handlers was at most 3.0 x 10-7 for the Enable® 2F formulation. Cancer risk associated with 

dermal exposure from harvesting and other activities occurring after application of the pesticide 

was estimated to be 1.4 x 10-7. 

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

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

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

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

appropriate review. 

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

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

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

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

2.0 HED Recommendations 

HED recommends in favor of an increased tolerance for residues of fenbuconazole on peppers, 

and addition of the use on peppers to the label for Enable® 2F. Additional data are needed, as 

outlined in Section 2.1. The specific tolerance recommendations are discussed in Section 2.2. 

2.1 Data Deficiencies 

There are no residue chemistry or exposure data deficiencies for fenbuconazole. 

An immunotoxicity study in the rat or mouse is required under the current 40 CRF Part 158. 

There are presently no other toxicology data deficiencies for fenbuconazole. HED has concluded 

that a rat 28- or 90-day inhalation toxicity, as well as acute and subchronic neurotoxicity studies, 

are not required based on consideration of the available toxicity data, chemical properties and 

registered and proposed use patterns. 

2.2 Tolerance Considerations 

HED has examined the residue chemistry database for fenbuconazole. There are no residue 

chemistry issues that would preclude increasing the tolerance for fenbuconazole on peppers. The 

HED-recommended tolerance is listed in Table 2.2.2. 
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2.2.1 Enforcement Analytical Method 

The available GC/NPD method, TR-34-90-47R, is considered adequate for tolerance 

enforcement and data collection purposes. 

2.2.2 Recommended Tolerances 

The tolerance expression proposed by the registrant is appropriate and includes the required 

coverage and compliance statements; therefore, the tolerance expression in 40 CFR §180.480 

should be revised to reflect the proposed language as follows: “Tolerances are established for 

residues of the fungicide fenbuconazole, 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 the sum of fenbuconazole, alpha–[2–(4–chlorophenyl)– ethyl]–

alpha–phenyl–3–(1H–1,2,4–triazole)– 1–propanenitrile, and its metabolites RH–9129, cis–5–(4–

chlorophenyl)– dihydro–3–phenyl–3–(1H–1,2,4– triazole–1–ylmethyl)–2–3 H–furanone, and 

RH–9130, trans–5–(4– chlorophenyl)-dihydro–3–phenyl–3– (1H–1,2,4–triazole–1–ylmethyl)–2–

3 H– furanone, calculated as the stoichiometric equivalent of fenbuconazole, in or on the 

following agricultural commodities.” 

Table 2.2.2. Tolerance Summary for Fenbuconazole. 

Commodity Established/Proposed 

Tolerance (ppm) 

HED-Recommended 

Tolerance (ppm) 

Comments 

(correct commodity definition) 

Pepper 0.4 ppm 1.0 ppm Commodity definition: Pepper 

2.2.3 Revisions to Petitioned-For Tolerances 

None 

2.2.4 International Harmonization 

As summarized in Appendix A, maximum residue limits (MRLs) for residues of fenbuconazole 

have been established by Codex, Canada and Mexico. The residue definition for both Codex and 

Mexico is parent fenbuconazole only, and the Canadian residue definition is the same as the U.S. 

tolerance definition which includes the parent and 2 metabolites. The Codex MRL for pepper is 

0.6 ppm and was most likely established before the Enable® 2F formulation was proposed for use 

on peppers, and includes only residues of the parent compound. This new formulation has 

higher residues values ranging up to 0.7 ppm, and the US tolerance includes the two lactone 

metabolites. Harmonization with the 0.6 ppm tolerance is not feasible given the proposed new 

use pattern/formulation. No Canadian or Mexican MRLs are established for fenbuconazole on 

peppers, and thus there are no harmonization issues in North America. 

2.3 Label Recommendations 

None

 
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3.0 Introduction

3.1 Chemical Identity

Table 3.1. Nomenclature of Fenbuconazole and its Regulated Metabolites

Compound 

Common name Fenbuconazole 

Company experimental names RH-7592 

IUPAC name (RS)-4-(4-chlorophenyl)-2-phenyl-2-(1H-1,2,4-triazol-1-ylmethyl)butyronitrile 

CAS name α-[2-(4-chlorophenyl)ethyl]-α-phenyl-1H-1,2,4-triazole-1-propanenitrile 

Chemical class Conazoles (triazoles) 

Molecular weight 336.8 

CAS registry number 114369-43-6 (119611-00-6, racemate) 

End-use products/EP 2 lb ai/gal FlC and 75% WPs 

Metabolite 

Common name cis lactone metabolite 

Company experimental names RH-9129 

IUPAC names (3R,5R)-5-(4-chlorophenyl)-3-phenyl-3-(1H-1,2,4-triazol-1-

ylmethyl)dihydrofuran-2(3H)-one 

CAS names cis-5-(4-chlorophenyl)dihydro-3-phenyl-3-(methyl-1-H,2,4-triazole-1-yl-2-(3H)-

furanone 

Molecular weight 353.8 

CAS registry number 146887-38-9 

Metabolite 

Common name trans lactone metabolite 

Company experimental names RH-9130 

N

N

N

Cl

CN

O

N

N

N

O

Cl

O

N

N

N

O

Cl
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Table 3.1. Nomenclature of Fenbuconazole and its Regulated Metabolites

IUPAC names (3S,5R)-5-(4-chlorophenyl)-3-phenyl-3-(1H-1,2,4-triazol-1-

ylmethyl)dihydrofuran-2(3H)-one 

CAS names trans-5-(4-chlorophenyl)dihydro-3-phenyl-3-(methyl-1-H,2,4-triazole-1-yl-2-

(3H)-furanone 

Molecular weight 353.8 

CAS registry number 146887-37-8 

3.2 Physical/Chemical Characteristics

Fenbuconazole is a triazole (conazole) fungicide. The physico-chemical properties are 

summarized in Appendix Table C.1. The vapor pressure is relatively low (0.37 x 10-7 mm Hg). 

Water solubility of fenbuconazole is low (3.8 mg/L), and it has a high octanol/water partition 

coefficient [Log(Kow) = 3.22]. Soil half-lives under both aerobic and anaerobic conditions are 

long (285 to 655 days), indicating that fenbuconazole is moderately persistent in the environment 

and slightly mobile into groundwater. 

3.3 Pesticide Use Pattern

Dow AgroSciences is proposing the first use of Enable® 2FTM (2.0 lbs ai/gallon, EPA Reg. No. 

62719-416) on peppers. The use directions, as provided in the existing labels and proposed 

supplemental labeling, are summarized below in Table 3.3. 

Table 3.3. Summary of Directions for Use of Fenbuconazole. 

Applic. Timing, Type, and 

Equip. 1 

Formulation 

[EPA Reg. 

No.] 

Applic. 

Rate 

(lb ai/A)

Max. No. 

Applic. per 

Season 

Max. Seasonal 

Applic. Rate 

(lb ai/A) 

PHI 

(days) Use Directions and Limitations 2 

Peppers (Including but not limited to: bell, chili, cooking, non-bell, pimento and sweet) 

Broadcast foliar 

applications to peppers 

when disease first appears 

Ground or aerial 

equipment 

75% WP 

[62719-421] 0.188 3 NS 0.75 7 

Apply in a minimum of 30 

gal/A, using ground equipment.

The minimum RTI is 10-14 

days. Do not make more than 2 

consecutive applications. 

Broadcast foliar 

applications to peppers 

when disease first appears 

Ground or aerial 

equipment 

2.0 lbs 

ai/gal. SC 

[62719-416] 

0.188 3

 NS 0.75 7 

Apply in a minimum of 30 

gal/A, using ground equipment.

The minimum RTI is 10-14 

days. Do not make more than 2 

consecutive applications. 1

 Do not apply through any type of irrigation system. Although application using aerial equipment is permitted, 

ground application is recommended. 2

 RTI = re-treatment interval. 

3 The maximum use rate is based on the use of 4 oz product/acre/application. 

NS = not specified. 

Note that rotational crop restrictions indicate that the minimum plant-back interval is 35 days 

when the last application of the product is <0.188 lb ai/A, and 210 days when the last application 
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of the product is 0.188-1.0 lb ai/A; this language appears on the proposed supplemental labeling 

for peppers, as well as on the main labels. 

The personal protective equipment (PPE) recommendations on the Indar® 75WSP and Enable®

2F labels indicate applicators and other handlers should wear a long-sleeved shirt and long pants, 

shoes plus socks, chemical-resistant gloves, and chemical-resistant headgear for overhead 

exposure. The restricted entry interval (REI) on the labels indicates workers may re-enter treated 

areas after 12 hours, which is appropriate based on the acute toxicity of technical fenbuconazole. 

Conclusions: The use directions are adequate to allow for evaluation of the residue data relative 

to the proposed formulation. The available field trial data and formulation bridging data on 

peppers are adequate and support the proposed use (4 oz product/A is equivalent to 0.188 lb 

ai/A). Although the single application rates used in the field trials were ~0.167 lb ai/A (0.9x 

rate), the residue data from these tests are adequate to support the 0.188 lb ai/A/application rate. 

3.4 Anticipated Exposure Pathways 

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

proposed revised tolerance for fenbuconazole on peppers, as well as addition of the use on 

peppers to the Enable® 2F label. Humans may be exposed to fenbuconazole in food and drinking 

water, since it may be applied directly to growing crops and application may result in 

fenbuconazole reaching surface and ground water sources of drinking water. There are no 

residential uses of fenbuconazole, so there is not likely to be exposure in residential or nonoccupational settings. In an occupational setting, applicators may be exposed while handling the 

pesticide prior to application, as well as during application. There is a potential for postapplication exposure for workers re-entering treated fields. 

Risk assessments have been previously conducted for fenbuconazole; toxicity data submitted 

prior to the last risk assessment but not incorporated into HED’s review have been evaluated in 

the current assessment, but did not affect HED’s conclusions with respect to hazard 

characterization and endpoint selection. A detailed description of the toxicity data and 

metabolism information may be found in the risk assessment dated 6/12/2008 (D. Dotson, 

D344351). The current risk assessment considers all of the aforementioned exposure pathways 

based on the existing uses of fenbuconazole, and also considers the potential for increased 

dietary exposure associated with the increased tolerance for residues in peppers.

The dietary endpoints and doses for fenbuconazole have not changed from the previous 

assessment. However, for occupational exposure assessment, the dose and endpoint selected for 

inhalation exposure and risk assessment has been revised. 

3.5 Consideration of Environmental Justice

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

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

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

(http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf. As a part of every pesticide risk 
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assessment, OPP considers a large variety of consumer subgroups according to well-established 

procedures. In line with OPP policy, HED estimates risks to population subgroups from 

pesticide exposures that are based on patterns of that subgroup’s food and water consumption, 

and activities in and around the home that involve pesticide use in a residential setting. 

Extensive data on food consumption patterns are compiled from the U.S. Department of 

Agriculture’s National Health and Nutrition Examination Survey, What We Eat in America, 

(NHANES/WWEIA) and are used in pesticide risk assessments for all registered food uses of a 

pesticide. These data are analyzed and categorized by subgroups based on age, season of the 

year, ethnic group, and region of the country. Additionally, OPP is able to assess dietary 

exposure to smaller, specialized subgroups and exposure assessments are performed when 

conditions or circumstances warrant. Whenever appropriate, non-dietary exposures based on 

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

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

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

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

workers as well as lifestyle and traditional dietary patterns among specific subgroups. 

4.0 Hazard Characterization and Dose-Response Assessment

Comprehensive risk assessments for fenbuconazole were conducted in 2006 (D316607; M. 

Collantes) and 2008 (D344351; D. Dotson). There are no changes to the endpoints or points of 

departure (PODs) for dietary assessment for acute, chronic or cancer risk used in the previous 

evaluations. However, the endpoint and dose selected for occupational inhalation exposure and 

risk assessment has been revised, reflecting changes in anticipated exposure scenarios and 

reevaluation of the endpoints observed in the rat 90-day study (see below, Section 4.3). 

Since the previous assessment, a supplemental metabolism study in the rat and a second 

developmental toxicity study in the rabbit (MRIDs 46473401 and 45259401, respectively) have 

been reviewed. These studies have been considered in this assessment but do not affect the 

endpoints selected or the overall evaluation of the toxicology findings. 

4.1 Summary of Toxicological Effects 

Subchronic and chronic feeding studies were conducted in the rat, mouse and dog. In these 

studies, the liver was the main target of toxicity in all three species. At lower dose levels in the 

subchronic studies, there were changes in liver histopathology, predominantly hepatocellular 

hypertrophy, along with increased liver weight. In the absence of other findings, these appeared 

to be adaptive liver changes, but at higher dose levels, frank liver toxicity was indicated by 

increases in liver enzymes (ALK, SGPT, SGOT). Increased hepatocellular vacuolization was 

observed at the higher dose levels as well, and in mice, hepatocellular necrosis was observed 

with a low incidence at the highest dose. In the rat, the thyroid was a secondary target organ 

with increased follicular cell size. In the chronic studies, liver effects were observed (including 

hepatocellular hypertrophy and vacuolization, changes in liver enzymes, and increased liver 

weights), as well as decreased body weight gains in all three species. Again, in the chronic rat 

study, the thyroid was a secondary target with increased thyroid and parathyroid weights and 

thyroid follicular cell hypertrophy. In addition, thyroid hormones were affected, with increased 
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mean T4 (thyroxine) and decreased TSH (thyroid stimulating hormone) being observed in the 

high-dose rats near the end of the study. In the chronic dog study, kidney and adrenal weights 

were also increased. Males and females throughout the studies appeared to be equally sensitive 

to fenbuconazole toxicity, except that male mice appeared to be more sensitive than the females 

after chronic exposure. 

In the rat and rabbit developmental toxicity studies and the two generation study in rats, all 

effects in the pups occurred in the presence of maternal toxicity, including changes in body 

weight and body weight gains in rats and decreased food consumption and clinical signs in 

rabbits. Developmental effects included increased post-implantation loss and decreased fetuses 

per dam in the rat developmental study; increased early resorptions in the rabbit developmental 

study; and decreased mean pup body weight, increased number of stillborn pups, decreased 

number of total offspring delivered, and decreased viability index of pups in the two generation 

study in rats. No increased qualitative or quantitative susceptibility was observed in any of the 

studies. There was no evidence of neurotoxicity in any of the studies available in the toxicology 

database. Therefore, a developmental neurotoxicity study is not required. 

Fenbuconazole is classified as a Group C or possible human carcinogen under the 1986 Agency 

Guidelines for assessing carcinogenicity based on an increased incidence of hepatocellular 

adenomas and carcinomas in male and female mice and thyroid follicular adenomas and 

combined adenomas/carcinomas in male rats. It has not been reevaluated under the current 

(2005) cancer guidelines, but may be reevaluated in the future as part of the ongoing Registration 

Review process. A cancer potency factor for quantification of risk was derived using combined 

hepatocellular adenomas/ carcinomas in female mice. The upper bound estimate of unit risk 

(Q1* (mg/kg/day)-1) is 3.59 x 10-3 in human equivalents. Fenbuconazole was not mutagenic in 

the available studies. 

Although fenbuconazole has a relatively high octanol:water coefficient and low solubility in 

water, dermal absorption was not significant and the majority of the radio-labeled compound 

could be recovered in a skin wash. Dermal penetration in the rat, evaluated using a 23% ai 

formulation product, was ≤4.25% measured after a 10 hour exposure. Consistent with these 

findings, no systemic toxicity was observed in the rat 28-day dermal toxicity study, and there 

was no dermal irritation at the application site. 

Fenbuconazole is extensively metabolized (19 metabolites identified or predicted) and rapidly 

excreted following single or repeated oral doses in the rat. Oxidation on the chlorophenol ring or 

the phenol ring, cyclization of the alcohol with the adjacent nitrile group and hydrolysis were 

observed. Glucuronide and sulfate conjugation of the hydroxyl groups also occurred. Cleavage 

of the triazole moiety was not a significant route of metabolism: very low levels of 1,2,4-triazole 

were observed in the urine (1.0 to 2.48% of dose). Metabolism was qualitatively similar in both 

sexes and appears to become saturated at higher dose levels. Excretion was primarily via the bile 

and feces, with low levels of radioactivity in the urine. Bioaccumulation was not observed. 

As summarized in Appendix Table B.2.1, acute studies were conducted on both the technical 

material and end-use product (25% a.i.). Technical grade fenbuconazole has low acute toxicity 

(Category III for acute oral and inhalation exposures and Category IV for acute dermal 
Fenbuconazole Human Health Risk Assessment DP No. D403041 

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exposure), as does the end-use product (Category III for acute inhalation exposure and Category 

IV for acute oral and dermal exposures). Neither is a skin or eye irritant (Category IV), or a 

dermal sensitizer. 

4.2 Safety Factor for Infants and Children (FQPA Safety Factor) 

HED has determined that the required 10X FQPA Safety Factor should be reduced to 1x in 

assessing the risk posed by fenbuconazole. This recommendation was based on the following 

considerations: 

• The toxicity data base is largely complete, with no data gaps for the assessment of the 

effects of fenbuconazole following in utero and/or postnatal exposure. 

• An immunotoxicity study is required for fenbuconazole, and is considered a data gap, 

however the existing database shows no evidence of immunotoxicity. 

• There is no evidence of neurotoxicity in the available database; acute and subchronic 

neurotoxicity studies are not available but were considered to be not required by 

HASPOC based on the lack of evidence of neurotoxicity in the database, and a 

developmental neurotoxicity study is not required. 

• There is no indication of quantitative or qualitative susceptibility of rats or rabbits to in 

utero and/or postnatal exposure to fenbuconazole. 

• The dietary exposure assessment is based on models and input parameters designed to be 

protective of human health. In addition, the dietary assessments are based on 

conservative inputs. 

• At this time, there are no registered residential uses for fenbuconazole. As a result, 

infants and children are not expected to be exposed through residential uses. 

4.2.1 Completeness of the Toxicology Database 

As summarized in Appendix Table B1, the toxicology database is considered adequate for the 

purpose of assessing pre- and postnatal susceptibility, lacking only an immunotoxicity study. 

However, no effects on the immune system were reported in the available studies and the 

conazole (triazoles), as a chemical class, typically do not demonstrate immunotoxic effects. 

Therefore, no additional database uncertainty factor for the lack of this study (UFDB) was 

applied. Acceptable developmental toxicity studies in the rat and rabbit and a rat reproductive 

toxicity study have been submitted. HED’s HASPOC (TXR #0056540) determined that acute 

and subchronic neurotoxicity studies in the rat are not required based on lack of evidence of 

neurotoxicity in the available studies. 

 

4.2.2 Evidence of Neurotoxicity 

The available studies did not show potential for neurotoxicity. There is no evidence for 

neurotoxicity in the existing database for fenbuconazole and the conazole fungicides as a group, 

which typically show either no evidence of neurotoxicity, or neurotoxicity at higher doses 

relative to the regulatory endpoints. A developmental neurotoxicity study is not required. 
Fenbuconazole Human Health Risk Assessment DP No. D403041 

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4.2.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal 

There is no evidence of increased qualitative or quantitative susceptibility in the developing or 

young animal and there are no residual uncertainties with respect to pre- or postnatal exposure. 

There are currently no registered or proposed residential uses for fenbuconazole, so exposure is 

limited to dietary exposure. 

4.2.4 Residual Uncertainty in the Exposure Database 

There is no residual uncertainty in the exposure database. There are no exposure data gaps and 

the current dietary exposure assessment is based on high-end assumptions such as field trial 

residue values and modeled estimates of drinking water residues. Therefore, the assessment is 

conservative and does not underestimate dietary exposure. 

4.3 Toxicity Endpoint and Point of Departure Selections 

The toxicological endpoints and points of departure selected for dietary and occupational 

exposure and risk assessment are presented below in Tables 4.3.1 and 4.3.2. The complete 

toxicological profile for fenbuconazole is summarized in Appendix Table B.2.2. There have been 

no changes to the dietary dose-response assessment or endpoints, the cancer classification/risk 

quantification or the occupational dermal assessment. 

A revised occupational exposure and risk assessment has not been conducted for this assessment 

since the use pattern has not changed with the addition of peppers to the label for the new 

formulation. For future occupational inhalation exposure assessments, the selected study and 

endpoint have changed. In the previous assessments, the rat combined chronic oral 

toxicity/carcinogenicity dietary study, with a NOAEL of 3 mg/kg/day, was selected as the 

critical study for all exposure durations, including long-term. Currently, occupational exposure 

of only short- or intermediate-term durations is anticipated. A 28- or 90-day inhalation study is 

not required. Since long-term occupational exposure is not anticipated, the oral studies of short 

or subchronic duration (rat, dog and mouse 90-day dietary; rat reproductive toxicity; rat and 

rabbit developmental toxicity) were considered for inhalation exposure. 

The NOAELs previously identified for the subchronic oral studies in rats, mice and dogs (M/F) 

were 1.3/1.5, 3.8/5/7 and 3.3/3.5 mg/kg/day, respectively. However, effects at the stated 

LOAELS identified for the rat, mouse and dog 90-day studies (5.1/6.3, 11.1/17.6 and 13.3/14.0 

mg/kg/day, respectively) were limited to liver hypertrophy and increased liver weight (in the 

dog, slight but not statistically significant increases in ALK were also observed at Week 13; 

significant changes were seen at the high dose). Based on current HED science policy, these 

changes are suggestive of an adaptive liver response and are not indicative of a clear adverse 

effect. At the next highest dose in each study (25.3/31.1, 28.6/50.4 and 50.4/53.3 mg/kg/day, 

respectively), altered liver enzymes indicated an adverse effect on the liver. Therefore, the 

NOAELs and LOAELs for these studies were reassigned to the next highest dose. For short- and 

intermediate-term inhalation exposure, the rat 90-day NOAEL of 5.1 mg/kg/day was selected 
Fenbuconazole Human Health Risk Assessment DP No. D403041 

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based on liver hypertrophy and clinical chemistry changes observed at the LOAEL of 25.3 

mg/kg/day. This endpoint is protective of developmental and reproductive effects, which were 

observed only at doses ≥40 mg/kg/day and for which NOAELs ranging from 4 to 30 mg/kg/day 

(developmental toxicity) were observed. Since an oral study was selected for assessing the 

inhalation route, toxicity via this route was considered to be equivalent to toxicity via the oral 

route, for the purpose of risk assessment. 

For all of the relevant routes and durations of exposure, clear NOAELs and LOAELs were 

identified. In addition, the toxicity database is considered to be largely complete, and no 

database uncertainty factors (UFs) were needed to account for missing data. With the reduction 

of the FQPA SF to 1X, the standard uncertainty factors of 100X (based on 10X for intraspecies 

variability and 10X for interspecies extrapolation) were applied. For inhalation risk assessment, 

the level of concern (LOC) is a margin of exposure (MOE) of 100. For dietary assessments, the 

combined UF of 100X was incorporated into the relevant reference doses (RfDs) and population 

adjusted doses (PADs). 

Table 4.3.1 Summary of Toxicological Doses and Endpoints for Fenbuconazole for Use in Dietary Health 

Risk Assessments 

Exposure/ 

Scenario 

Point of 

Departure 

Uncertainty/FQPA 

Safety Factors 

RfD, PAD, 

Level of 

Concern for 

Risk 

Assessment 

Study and Toxicological Effects

Acute Dietary 

(General 

Population, 

including 

Infants and 

Children) 

An appropriate dose and endpoint were not identified for this population group. 

Acute Dietary 

(Females 13-

49 years of 

age) 

NOAEL = 

30 

mg/kg/day 

UFA= 10x 

UFH=10x 

FQPA SF= 1x 

Acute RfD = 

0.3 mg/kg/day 

Acute PAD= 

0.3 mg/kg/day 

Developmental rat study

Developmental LOAEL = 75 mg/kg/day 

based on increased resorptions and 

decreased live fetuses per dam. 

Chronic 

Dietary (All 

Populations) 

NOAEL= 3 

mg/kg/day 

UFA= 10x 

UFH=10x 

FQPA SF= 1x 

Chronic RfD = 

0.03 

mg/kg/day 

cPAD = 0.03 

mg/kg/day 

Combined chronic toxicity/ 

carcinogenicity - Rat

LOAEL = 30.6/43.1 (M/F) mg/kg/day 

based on decreased body weight gain, 

increased thyroid weight, and 

histopathological lesions in the liver and 

thyroid gland 

Cancer (oral, 

dermal, 

inhalation) 

Classification: Group C, probable human carcinogen. This classification is based on increased 

incidence of hepatocellular adenomas and carcinomas in male and female mice and thyroid 

follicular adenomas and combined adenomas/carcinomas in male rats. Quantification of risk was 

derived using combined hepatocellular adenomas/carcinomas in female mice. The upper bound 

estimate of unit risk, Q1* (mg/kg/day)-1 is 3.59 x 10-3 in human equivalents. 

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 
Fenbuconazole Human Health Risk Assessment DP No. D403041 

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sensitivity among members of the human population (intraspecies). FQPA SF = FQPA Safety Factor. PAD = 

population adjusted dose (a = acute, c = chronic). RfD = reference dose. N/A = not applicable.

Table 4.3.2 Summary of Toxicological Doses and Endpoints for Fenbuconazole for Use in Occupational 

Human Health Risk Assessments 

Exposure/ 

Scenario 

Point of 

Departure 

Uncertainty 

Factors 

Level of Concern 

for Risk 

Assessment 

Study and Toxicological Effects 

Dermal 

All Durations No endpoint of concern was identified, based on a lack of hazard via the dermal route. 

Inhalation 

Short-Term (1-

30 days) and 

Intermediateterm (1-6 

months) 

Oral study 

NOAEL= 5.1 

mg/kg/day 

[Inhalation 

toxicity assumed 

equivalent to oral 

toxicity] 

UFA=10x 

UFH=10x 

Occupational LOC 

for MOE = 100 90-day oral toxicity - Rat

LOAEL = 25.3/31/1 (M/F) 

mg/kg/day based on decreased 

body weight gain, clinical 

chemistry changes, and 

histopathological lesions in the 

liver and thyroid gland. 

Cancer (oral, 

dermal, 

inhalation) 

Classification: Group C, probable human carcinogen. This classification is based on 

increased incidence of hepatocellular adenomas and carcinomas in male and female mice and 

thyroid follicular adenomas and combined adenomas/carcinomas in male rats. Quantification of 

risk was derived using combined hepatocellular adenomas/carcinomas in female mice. The upper 

bound estimate of unit risk, Q1* (mg/kg/day)-1 is 3.59 x 10-3 in human equivalents. 

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). MOE = margin of exposure. LOC = level of 

concern. N/A = not applicable.

5.0 Dietary Exposure and Risk Assessment 

5.1 Residues of Concern Summary and Rationale 

HED has previously considered the residues of concern for both risk assessment and tolerance 

enforcement, based on the results of acceptable metabolism studies. HED has determined that 

the residues of concern for risk assessment are fenbuconazole and the following metabolites: 

RH-9129, RH-9130, RH-4911(peanut only), and RH-7905 (peanut only). RH-9129 and RH9130 are cis/trans isomers of the lactone metabolite of fenbuconazole and may account for 

approximately one third of the total fenbuconazole residues. RH-9129 and RH-9130 are residues 

of concern for both risk-assessment and tolerance-enforcement purposes. RH-7905 is a minor 

metabolite except in peanut. In animals, the glucoside conjugate (RH-7905) will be cleaved to 

yield RH-4911. Although RH-4911, a hydroxy-derivative of fenbuconazole, is likely to be less 

toxic than the parent, there is no specific toxicological information for this compound. Because 

it shares structural features with the parent, HED has assumed it has the same toxicity as 

fenbuconazole. Therefore, RH-7905 and RH-4911 have been included as residues of concern for 

risk assessment (peanuts only). The current analytical enforcement method has been validated 

for the analysis of fenbuconazole as well as RH-9129 and RH-9130. 
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Another metabolite, the iminolactone metabolite (RH-6468) is also be included de facto in the 

residues of concern, because it is converted to the lactones by the analytical method, and would 

be included in the measured residues. 

Drinking Water 

The estimated drinking water concentrations (EDWCs) used in the dietary risk assessments were 

provided by the Environmental Fate and Effects Division (EFED, D344352, J. Lin, 1/16/2008). 

The EDWCs were incorporated directly into these dietary assessments in the food categories 

“water, direct, all sources” and “water, indirect, all sources.” The EDWCs for fenbuconazole 

were generated with the coupled models PRZM and EXAMS for surface water and SCI-GROW 

for groundwater. Modeled surface water EDWCs are based on the maximum label application 

rate to peppers (acute value) or cherries (chronic and cancer values). The groundwater EDWC is 

based on the maximum label application rate to cherries. EDWCs reflect exposure to 

fenbuconazole. The common triazole metabolites 1,2,4-triazole, triazole alanine, and triazole 

acetic acid have been identified as residues of concern for risk assessment. A separate dietary 

exposure assessment has been performed for these metabolites (D403618, T. Morton). As a 

result, they are not being included in this assessment. 

The PRZM/EXAMS 1-in-10 year annual peak surface water value of 24.1 ppb for peppers is 

greater than the SCI-GROW groundwater value of 0.031 ppb. As a result, the surface water 

value was used in the acute dietary analysis. The 1 in 10 year annual mean surface water value 

of 16.5 ppb for cherries is greater than the groundwater value of 0.031 ppb. As a result, the 

surface water value was used in the chronic dietary analysis. Finally, the 30-year annual mean 

surface water value of 11.7 ppb for cherries is greater than the groundwater value of 0.031 ppb. 

As a result, the surface water value was used in the cancer dietary analysis. The SCI-GROW 

Model and its description are available at the EPA internet site: 

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

Table 5.1. Summary of Metabolites and Degradates to be included in the Risk Assessment and Tolerance 

Expression* 

Matrix Residues included in Risk 

Assessment 

Residues included in Tolerance 

Expression 

Plants Primary Crop Fenbuconazole + RH-9129 + RH9130 + RH-7905 (peanut only) + 

RH-4911 (peanut only) 

Fenbuconazole + RH-9129 + RH-9130, 

expressed as fenbuconazole

Rotational Crop Not Applicable Not Applicable 

Livestock Ruminant Fenbuconazole + RH-9129 + RH9130 Fenbuconazole + RH-9129 + RH-9130, 

expressed as fenbuconazole 

Poultry Not Applicable Not Applicable 

Drinking Water Fenbuconazole Not Applicable 

* The common triazole metabolites 1,2,4-triazole, triazolylalanine, and triazolylacetic acid have been identified as 

residues of concern for risk assessment. Separate assessments addressing these compounds have been conducted 

(see. T. Morton, D403618). 

 
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5.2 Food Residue Profile 

The qualitative nature of fenbuconazole residues in plants and livestock is adequately understood 

Based on acceptable metabolism studies in peaches, peanuts, sugar beets, and wheat. In addition 

to the fenbuconazole residues of concern for risk assessment and tolerance enforcement, HED 

has considered the potential for exposure to the triazole metabolites 1,2,4-triazole, triazole 

alanine, and triazole acetic acid as a result of fenbuconazole use. The free triazole and its 

conjugates are considered to be residues of concern for risk assessment for all triazole-derivative 

fungicides. While HED does not set tolerances for these metabolites, a separate dietary and 

aggregate assessment is conducted when new uses of triazole-derivative fungicides have the 

potential to increase exposure to free triazole and its conjugates. 

There are no livestock feedstuffs associated with the use on peppers and the proposed increased 

tolerance; therefore, data requirements for livestock metabolism and feeding studies are not 

relevant to this tolerance petition. However, livestock tolerances have been established in 

conjunction with other crop uses of fenbuconazole, and the data supporting the established 

livestock tolerances are adequate. 

There are adequate data for risk assessment and tolerance assessment. There were finite residues 

of the parent compound in/on peppers in the bridging study, and there were very low levels or 

non-detectable levels of the metabolite RH-9129. Residue levels for the RH-9130 metabolite 

were all below the limit of detection (LOD). Residues of the parent compound tended to decline 

with increasing pre-harvest interval (PHI) with an estimated half-life of between 8 to 9 days. 

Residue data are summarized below. 

5.2.1 Crop Field Trials (860.1500) 

D390352, S. Oonnithan, 9/8/2011 

Bridging Data

Dow AgroSciences has submitted a bridging study on pepper to translate residues from Indar®

75WSP to Enable® 2F, thereby obviating the need for a full field trial data set for use of the 

Enable® 2F formulation on peppers. 

The bridging study conducted on bell pepper consisted of side-by-side trials in six locations, in 

which both formulations were applied to peppers. The submitted residue data (6 samples) for the 

WP and SC formulations were analyzed using the OECD MRL calculation procedures for the 

purpose of comparing the data sets from the previously reviewed field trials used to establish the 

existing tolerance and the new bridging data. The results of the comparison are shown below: 

 
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Table 5.2.1a. Fenbuconazole Total Residue1

Indar® WSP 

2008 Data 

Indar® WSP 

Bridging Study 

Enable® 2F 

Bridging Study 

Current or recommended tolerance 0.40 0.70 1.0 

 Lowest residue 0.05 0.029 0.044 

 Highest residue 0.22 0.465 0.668 

 Mean residue 0.136 0.142 0.189 

 No. of samples (avg. of 2 replicates) 18 6 6 

1

See D390352, S. Oonnithan, 8 Sept 2011.

Conclusions: Although the submitted bridging residue data on pepper using the WP (Indar®) 

and SC (Enable® 2F) formulations of fenbuconazole are limited, the results summarized above 

indicate the potential for significantly higher residues of fenbuconazole than found in the earlier 

field trials, even for the existing formulation. Based on the submitted data, the current 0.40 ppm 

tolerance does not support the higher residues found on pepper with either the WP formulation or 

the SC formulation. Therefore, the existing tolerance should be increased to 1.0 ppm to support 

use of the SC formulation. HED notes that the residue values for bell and non-bell peppers in the 

original submission were very similar (MRID 47215801); therefore the use of only bell peppers 

in the bridging study is not an issue. 

Triazole Metabolites 

Residues of 1,2,4-triazole and triazole acetic acid were non-detectable (<0.003 ppm) in all 

treated pepper samples. Triazole alanine residues ranged from 0.0187 to 0.158 ppm in treated 

peppers. Untreated control pepper samples also had triazole alanine residues which ranged from 

0.0029 to 0.013 ppm. Table 5.2.1b lists the results from the triazole metabolite analyses and is 

taken directly from the study report. 
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 Table 5.2.1b. Bell Pepper Field Trial Data for Fenbuconazole (Triazole Metabolites). 

Residue Found in PPMc

Trial 

Identification 

(variety) 

Ratea Sampling 

Intervalb

(days) 

Test 

Substance 

Triazole Triazole 

alanine 

Triazole 

acetic acid 

Tallassee, AL 

(King Arthur) 4 x 0.188 7 

Enable ND 

ND 

0.0191 

0.0213 

ND 

<LOD 

Indar <LOD 

<LOD 

0.0187 

0.0195 

<LOD 

ND 

Shady Grove, FL 

(Aristotle) 4 x 0.188 7 

Enable <LOD 

<LOD 

0.0289 

0.0265 

<LOD 

<LOD 

Indar <LOD 

<LOD 

0.0228 

0.0244 

<LOD 

<LOD 

Stewardson, IL 

(Better Bell) 4 x 0.188 7 

Enable ND 

ND 

0.0226 

0.024 

<LOD 

<LOD 

Indar ND 

ND 

0.0325 

0.0309 

<LOD 

<LOD 

Uvalde, TX 

(Camelot) 4 x 0.188 7 

Enable <LOD 

ND 

0.0247 

0.0244 

ND 

ND 

Indar ND 

ND 

0.0268 

0.0268 

ND 

ND 

Visalia 

(Cypress) 4 x 0.188 7 

Enable <LOD 

ND 

0.0297 

0.0287 

<LOD 

ND 

Indar <LOD 

<LOD 

0.0220 

0.0237 

ND 

<LOD 

Sanger, CA 

(Cypress) 

4 x 0.188 0 

Enable <LOD 

<LOD 

0.106 

0.099 

<LOD 

<LOD 

Indar <LOD 

ND 

0.136 

0.144 

<LOD 

<LOD 

4 x 0.188 3 

Enable ND 

ND 

0.107 

0.116 

<LOD 

<LOD 

Indar <LOD 

<LOD 

0.158 

0.149 

<LOD 

<LOD 

4 x 0.188 7 

Enable ND 

ND 

0.090 

0.084 

<LOD 

<LOD 

Indar ND 

<LOD 

0.130 

0.102 

<LOD 

<LOD 

4 x 0.188 10 

Enable ND 

ND 

0.095 

0.104 

<LOD 

<LOD 

Indar ND 

ND 

0.147 

0.143 

<LOD 

<LOD 

4 x 0.188 14 

Enable ND 

ND 

0.102 

0.106 

<LOD 

<LOD 

Indar ND 

ND 

0.126 

0.128 

<LOD 

<LOD 

(a) Four foliar broadcast applications were made at 0.188 lb ai/A each time for a total treatment rate of 0.752 lb ai/A. 

(b) Sampling Interval is the days from the last application. 

(c) Individual residue levels are shown for each of the two replicates samples collected from each treatment plot. The LOD is 0.003 ppm 

and the LOQ is 0.01 ppm. ND is no chromatographic response. 

Conclusions: There were no significant differences in triazole metabolite residue level resulting 

from treatment with either formulation. Residues of 1,2,4-triazole and triazole acetic acid were 

all non-detectable. Residues of triazole alanine averaged 0.025 ppm, while the maximum 

observed residue for triazole alanine was 0.158 ppm. These triazole metabolites have been 

addressed in a separate risk assessment, but ultimately do not impact HED’s estimate of 

aggregate exposure and risk from free triazole, triazole alanine and triazole acetic acid. 
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5.2.2 Field Rotational Crops (860.1900) 

D259204, S. Oonnithan, 7/25/06

An adequate confined rotational crop study is available indicating that the metabolite profile for 

fenbuconazole in rotational crops is similar to the metabolism in primary crops. Limited 

rotational crop field trials and rotational crop tolerances are not required provided labels continue 

to specify a minimum PBI of 35 days following the last application to peppers of ≤0.188 lb ai/A, 

and a minimum PBI of 210 days following a last application of 0.188 - 1.0 lb ai/A. 

 

5.2.3 Processed Food and Feed (860.1520) 

HED does not require residue data for any processed commodities associated with peppers. 

Therefore, data requirements for processed food and feed are not relevant to the currently 

proposed increased tolerance. 

5.3 Water Residue Profile 

Drinking Water Exposure Assessment for Fenbuconazole Use on Pepper, D344352, J. Lin, 1/16/2008 

Fenbuconazole is considered to be moderately persistent to persistent in the environment and 

slightly mobile to mobile in soils. Because of its adsorption to soil, the potential for 

fenbuconazole to leach to groundwater appears to be slight. However, the potential to 

contaminate groundwater may be greater at vulnerable sites, i.e., where soils have low organic 

matter and where groundwater is relatively close to the surface. For purposes of human health 

risk assessment, the residue of concern in water is fenbuconazole. 

RH-9129, RH-9130, RH-6467, and RH-0118 (1,2,4-triazole) are degradates of fenbuconazole. 

In the aerobic metabolism study, concentrations of the metabolites RH-9129, RH-9130, and RH6467 increased with time accounting for 2.5-9.6% of the applied radioactivity in both soils 

treated with both radiolabels (RH-9129 and RH-9130 are diastereomers). 1,2,4-Triazole 

accounted for 11.2-13.6% and for 6.5-6.6% of the applied 14C-triazole-RH-7592 in the 

Lawrenceville and Pasquotank soils, respectively. In the anaerobic metabolism study, RH-9129 

and combined RH-9130/RH-6467 accounted for 0.6% (day 0) to 7.33% (day 60). 

Given that the use pattern for peppers has not changed, HED used the drinking water assessment 

used in the last risk assessment for peppers. The estimated drinking water concentrations 

(EDWCs) used in the dietary risk assessments were provided by the Environmental Fate and 

Effects Division (EFED, D344352, J. Lin, 1/16/2008) and are summarized below in Table 5.3. 

The EDWCs were incorporated directly into these dietary assessments in the food categories 

“water, direct, all sources” and “water, indirect, all sources.” The EDWCs for fenbuconazole 

were generated with the coupled models PRZM and EXAMS for surface water and SCI-GROW 

for groundwater. Modeled surface water EDWCs are based on the maximum label application 

rate to peppers (acute value) or cherries (chronic and cancer values). The groundwater EDWC is 

based on the maximum label application rate to cherries. These EDWCs reflect concentrations 

of fenbuconazole-specific residues. The common triazole metabolites 1,2,4-triazole, triazole 

alanine, and triazole acetic acid have separate EDWCs and have been included in HED’s 

aggregate assessment for free triazole and its conjugates. 
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The PRZM/EXAMS-generated drinking water estimates for surface water sources of drinking 

water were all greater than those generated by the SCI-GROW model for groundwater sources of 

drinking water. Therefore, HED relied on surface water estimates, which are protective of 

exposure from both ground and surface water sources. The 1-in-10-year annual peak surface 

water value of 24.1 ppb was used in the acute assessment; the 1-in-10-year annual mean surface 

water value of 16.5 ppb used in the chronic non-cancer dietary analysis. The 30-year annual 

mean surface water value of 11.7 ppb was used in the cancer dietary analysis. The drinking 

water models and descriptions are available at the EPA internet site: 

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

Table 5.3 Summary of Estimated Surface Water and Groundwater Concentrations for 

Fenbuconazole.

Scenario Surface Water Conc., ppb a Groundwater Conc., ppb b

Acute 24.1 0.031 

Chronic (non-cancer) 16.5 0.031 

Chronic (cancer) 11.7 0.031 

a

 From the Tier II PRZM-EXAMS - Index Reservoir model. Input parameters are based on maximum label 

application rate to cherries for the chronic assessments, and for peppers for the acute assessment. 

b

 From the SCI-GROW model. 

Data taken from EFED Drinking Water Assessment, D344352, J. Lin, 1/16/2008. 

5.4 Dietary Risk Assessment 

5.4.1 Description of Residue Data Used in Dietary Assessment 

For peppers, the HED-recommended tolerance level of 1.0 ppm was used as the residue value in 

the acute dietary exposure analysis. The average field trial value of 0.19 ppm for peppers from 

the Enable® 2F bridging study was used for the chronic and cancer dietary exposure analyses. 

Residue values used for all other commodities are discussed in detail in the previous dietary 

exposure memo completed for fenbuconazole (D350321, D. Dotson, 6/12/2008). Tolerances for 

fenbuconazole are listed in 40CFR§180.480. The acute and chronic assessments are based on 

100% crop treated assumptions for all commodities. 

The residue estimates used in these assessments are directly from the field trial data and, by 

nature of the analytical methods, account for all of the fenbuconazole-specific residues of 

concern in crops and livestock. A separate dietary exposure assessment has been performed for 

the common triazole metabolites (D403618, T. Morton). Crop field trials resulted in measurable 

fenbuconazole residues of concern for all crops. 

Acute Assessment. The acute dietary (food + water) assessment is a screening-level assessment. 

It is based on tolerance-level residues for all foods, assumes 100% crop treated, and the acute 

estimated drinking water concentration (EDWC) for fenbuconazole in surface water (24.1 ppb), 

which is a high-end estimate derived from the use pattern for peppers. The acute assessment 

includes DEEMTM Version 7.81 default processing factors for those commodities that were not 
Fenbuconazole Human Health Risk Assessment DP No. D403041 

Page 23 of 43

addressed by the available processing studies. For commodities where there are data indicating 

that residues do not concentrate during processing, a factor of one was used to be protective. 

Chronic (Non-cancer) and Cancer Assessments. The chronic (non-cancer) and cancer dietary 

assessments include contributions from both food and water. The chronic estimated drinking 

water concentration (EDWC) for fenbuconazole is the 1-in-10-year annual mean surface water 

value of 16.5 ppb in surface water, which is a high-end estimate derived from the use on cherries. 

The cancer estimated drinking water concentration (EDWC) is the 30-year annual mean surface 

water value of 11.7 ppb for cherries, which is also a high-end estimate derived from the use on 

cherries. For many crops average residue values were used. The chronic assessments use 

DEEMTM version 7.81 default processing factors for commodities that do not have empirical 

processing factors. The non-cancer assessment assumes 100% crop treated, whereas the cancer 

assessment makes use of average percent-crop-treated estimates. The following percent crop 

treated estimates were used in the cancer dietary risk assessment for the following crops that are 

currently registered for fenbuconazole: almonds: 5%, Apples: 5%, apricots: 5%, blueberries: 

55%, cherries: 15%, grapefruit: 40%, nectarines: 5%, oranges: 5%, peaches: 15%, pecans: 10%, 

plums/prunes: 1%, sugar beets: 1%, tangelos: 10%, tangerines: 1%. 

5.4.2 Percent Crop Treated Used in Dietary Assessment 

Screening Level Estimates of Agricultural Uses (SLUA) for the Fungicide Fenbuconazole (129011), Sepehr 

Haddad, 11/13/2012. 

The acute and non-cancer chronic dietary assessments are based on 100% crop treated 

assumptions for all commodities. 

The following average percent crop treated estimates (Screening Level Estimates of Agricultural 

Uses (SLUA) for the Fungicide Fenbuconazole (129011), Sepehr Haddad, 11/13/2012) were 

used in the cancer dietary risk assessment for the following crops that are currently registered for 

fenbuconazole: almonds: 5%, apples: 5%, apricots: 5%, blueberries: 55%, cherries: 15%, 

grapefruit: 40%, nectarines: 5%, oranges: 5%, peaches: 15%, pecans: 10%, plums/prunes: 1%, 

sugar beets: 1%, tangelos: 10%, tangerines: 1%. 

5.4.3 Acute Dietary Risk Assessment 

Females Age 13-49 were assessed for acute dietary risk; no endpoints of concern were identified 

for the general population including infants and children. No risks of concern were identified for 

acute dietary exposure. The results of the acute dietary exposure analysis for females 13-49 

years of age at the 95th, 99th, and 99.9th percentiles of exposure are reported in Table 5.4.3. As 

percent crop treated estimates were not used in the acute assessment, HED recommends that the 

95th percentile of exposure be used for regulation. The population subgroup Females 13-49 

utilizes 2.9% of the aPAD at the 95th percentile of exposure. 

 
Fenbuconazole Human Health Risk Assessment DP No. D403041 

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Table 5.4.3. Results of Acute Dietary Exposure Analysis (Food and Drinking Water)

Population Subgroup 

aPAD 

(mkd)* 

95th Percentile 99th Percentile 99.9th Percentile 

Exposure 

(mkd) 

% 

aPAD 

Exposure 

(mkd) 

% 

aPAD 

Exposure 

(mkd) 

% 

aPAD 

Females 13-49 years old 0.30 0.008618 2.9 0.013971 4.66 0.026168 8.72 

*mkd: milligram per kilogram body weight per day

5.4.4 Chronic Dietary Risk Assessment 

All populations were evaluated for chronic dietary risk. No risks of concern were identified in 

the chronic dietary exposure analysis. The most highly exposed population subgroup is children 

1-2 years old which utilizes 6.7% of the cPAD (Table 5.4.6). The general U.S. population 

utilizes 2.3% of the cPAD. 

5.4.5 Cancer Dietary Risk Assessment 

Cancer risk is determined for the general U.S. population only. Applying the Q1* value of 

0.00359 (mg/kg/day)-1 to the exposure value of 0.000604 mg/kg/day yields a cancer risk estimate 

of 2.2 x 10-6 (Table 5.4.6). Although the cancer risk assessment incorporated estimates of %CT 

and the use of average field trial data, the cancer risk estimate could be further refined with the 

use of monitoring data, and actual cancer risk is expected to be lower than the value presented in 

the table below. 

5.4.6 Summary Table 

The results of the dietary exposure and risk analyses for acute and chronic dietary exposures, and 

for cancer risk, are summarized below in Table 5.4.6. 

Table 5.4.6. Summary of Dietary Exposure and Risk for Fenbuconazole (Food and Drinking 

Water)

Population Subgroup* 

Acute Dietary 

(95th Percentile) Chronic Dietary Cancer 

Dietary 

Exposure 

(mg/kg/day) % aPAD 

Dietary 

Exposure 

(mg/kg/day) % cPAD 

Dietary 

Exposure 

(mg/kg/day) Risk 

General U.S. Population N/A N/A 0.000705 2.3 

0.000604 2.2 x 10-6

All Infants (< 1 year old) N/A N/A 0.001755 5.8 

Children 1-2 years old N/A N/A 0.002018 6.7 

Children 3-5 years old N/A N/A 0.001410 4.7 

Children 6-12 years old N/A N/A 0.000796 2.7 

Youth 13-19 years old N/A N/A 0.000458 1.5 

Adults 20-49 years old N/A N/A 0.000587 2.0 

Adults 50-99 years old N/A N/A 0.000652 2.2 

Females 13-49 years old 0.008618 2.9 0.000602 2.0 

 
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6.0 Residential (Non-Occupational) Exposure/Risk Characterization

There are presently no residential uses for fenbuconazole.

6.5 Residential Bystander Post-application Inhalation Exposure 

Based on the Agency's current practices, a quantitative post-application inhalation exposure 

assessment was not performed for fenbuconazole at this time primarily because of the low acute 

inhalation toxicity (Toxicity Category III and IV), low vapor pressure (at 25o C, 3.7 x10-8 mm 

Hg at 25C), and the low proposed use rate (0.188 lb ai/A). However, volatilization of pesticides 

may be a source of post-application inhalation exposure to individuals nearby pesticide 

applications. The Agency sought expert advice and input on issues related to volatilization of 

pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel 

(SAP) in December 2009, and received the SAP’s final report on March 2, 2010 

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

process of evaluating the SAP report and may, as appropriate, develop policies and procedures to 

identify the need for and, subsequently, the way to incorporate post-application inhalation 

exposure into the Agency's risk assessments. If new policies or procedures are developed, the 

Agency may revisit the need for a quantitative post-application inhalation exposure assessment 

for fenbuconazole. 

6.6 Spray Drift 

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

This is particularly the case with aerial applications allowed on fenbuconazole labels, but, to a 

lesser extent, could also be a potential source of exposure from ground application methods 

employed for fenbuconazole. The Agency has been working with the Spray Drift Task Force, 

EPA Regional Offices and State Lead Agencies for pesticide regulation and other parties to 

develop the best spray drift management practices (see the Agency’s Spray Drift website for 

more information at http://www.epa.gov/opp00001/factsheets/spraydrift.htm). On a chemical by 

chemical basis, the Agency is now requiring interim mitigation measures for aerial applications 

that must be placed on product labels/labeling. The Agency has completed its evaluation of the 

new database submitted by the Spray Drift Task Force, a membership of U.S. pesticide 

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

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

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

spray drift management practices to reduce off-target drift with specific products with significant 

risks associated with drift. 

Although a quantitative residential post-application inhalation exposure assessment was not 

performed as a result of pesticide drift from neighboring treated agricultural fields, an inhalation 

exposure assessment was performed for flaggers. This exposure scenario is representative of a 

worse case inhalation (drift) exposure and may be considered protective of most outdoor 

agricultural and commercial post-application inhalation exposure scenarios. 

 
Fenbuconazole Human Health Risk Assessment DP No. D403041 

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7.0 Aggregate Exposure/Risk Characterization

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

risks from three major sources: food, drinking water, and residential exposures. In an aggregate 

assessment, exposures from relevant sources are added together and compared to quantitative 

estimates of hazard (e.g., a NOAEL or PAD), or the risks themselves can be aggregated. When 

aggregating exposures and risks from various sources, HED considers both the route and 

duration of exposure. 

7.1 Acute & Chronic Aggregate Risk 

Acute and chronic (both cancer and non-cancer) aggregate exposures include food plus drinking 

water exposures. As demonstrated under Section 5.4, acute and chronic aggregate risks are not 

of concern. 

7.2 Short- and Intermediate-Term Aggregate Risk

Short-and intermediate-term aggregate exposures take into account residential exposure plus 

average exposure levels to food and water (considered to be a background exposure level). For 

fenbuconazole, there are no residential uses, and therefore a short-term aggregate risk assessment 

was not needed. 

Updated Aggregate Assessment of Free Triazole & its Conjugates

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

to Address The Amended Propiconazole Section 3 Registration to Add Use on Sugarcane.

DP403619, T. Morton, 8/1/12.

The addition of the proposed amended use does not increase the aggregate exposure to free 

triazole and its conjugates. Therefore, the most recent aggregate human health risk assessment 

for free triazole and its conjugates, which indicated the aggregate estimates are below HED’s 

level of concern (D403619, T. Morton, 8/1/12), is also protective of potential aggregate exposure 

and risk associated with this tolerance action for fenbuconazole. 

8.0 Cumulative Exposure/Risk Characterization

Fenbuconazole is a member of the triazole-containing class of pesticides. Although conazoles 

act similarly in 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 conazoles are hepatotoxic and hepatocarcinogenic in mice. Some induce thyroid 
Fenbuconazole Human Health Risk Assessment DP No. D403041 

Page 27 of 43

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. 

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

metabolite 1,2,4-triazole and two triazole conjugates (triazolylalanine and triazolylacetic acid). 

To support existing tolerances and to establish new tolerances for triazole-derivative pesticides, 

including fenbuconazole, U.S. EPA conducted a human health risk assessment for exposure to 

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

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

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

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

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

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

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

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

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

9.0 Occupational Exposure/Risk Characterization

Detailed occupational exposure and risk characterizations for the use of both product 

formulations containing fenbuconazole have previously been conducted. Both product 

formulations were previously assessed for handler exposures, for similar scenarios. Indar® 75 

WSP was evaluated for use on pepper and other crops (S. Wang, D345898, 5/28/2008) and 

Enable® 2F was assessed for use on cranberry, peanut, and other crops (D28908, M. Collantes, 

6/26/2006). Both assessments used the same single application rates (0.19 lb ai/A), equipment 

(ground and aerial foliar), timing (10 day interval), and number of applications (4) as are 

currently proposed for the label amendment for peppers. 

HED has taken into consideration the findings of the previous risk assessment for peppers and 

the similarities between the use pattern of the existing and proposed formulations, and has 

determined that new occupational exposure and risk assessments are not needed to ensure 

adequate protection of occupational workers mixing, loading and applying the fungicide. 

Comparison of Use Pattern 

Indar® 75 WSP is registered for use on pepper (including bell, chili, cooking, pimento, and sweet 

varieties) at single and seasonal maximum application rates of 0.188 and 0.75 lb ai/A, 

respectively. The label allows a maximum of 4 applications occurring at10 day intervals; 

however, the label prohibits more than 2 consecutive applications of fenbuconazole, in order to 
Fenbuconazole Human Health Risk Assessment DP No. D403041 

Page 28 of 43

prevent development of resistance. The pre-harvest interval (PHI) is 7 days after the last 

application. The registrant is proposing the same use pattern for Enable® 2F on pepper. 

The personal protective equipment (PPE) specified on the Indar® 75 WSP label includes baseline 

clothing (long sleeved shirt, long pants and shoes with socks), chemical resistant gloves, and 

chemical resistant head gear for overhead exposure. The same PPE recommendations are 

specified on the proposed label for Enable® 2F. 

Both labels have the same restricted-entry interval (REI) of 12 hours, which is based on the acute 

toxicity of the technical active ingredient. Exposure (dermal and inhalation) is expected to be of 

short- or intermediate-term duration for all scenarios. Long-term occupational exposure is not 

anticipated, either from dermal or inhalation routes. 

Occupational Handler Assessments

In the previous assessments, dermal risks were not assessed quantitatively due to the lack of 

systemic toxicity via the dermal route, and in the absence of developmental or reproductive 

effects that would not have been assessed in the dermal study. 

For inhalation exposure, the previous assessment used the dose and endpoint from the rat chronic 

oral study (liver and thyroid effects), in the absence of a route-specific inhalation toxicity study. 

In conjunction with the current risk assessment, HED’s HASPOC determined that a subchronic 

inhalation toxicity study is not needed for fenbuconazole (TXR No. 0056540). For the current 

assessment, a new occupational inhalation exposure assessment is not needed; however in the 

future, the dose and endpoint for inhalation exposure will be taken from the 90-day rat study. 

Since the 90-day no-observed-adverse-effects-level (NOAEL) and lowest-observed-adverseeffects-level (LOAEL) are slightly higher than in the chronic study, HED’s risk estimates for 

inhalation exposure will be lower. 

As stated previously, quantitative non-cancer dermal risk assessments were not needed due to the 

lack of toxicity via the dermal route. For Indar® 75 WSP on pepper, the estimated short-term 

non-cancer inhalation risk for handlers was an MOE greater than or equal to 9,100 assuming the 

use of baseline PPE; the MOEs were greater than 100 and are therefore not of concern. 

Combined dermal and inhalation cancer risk for occupational handlers was estimated to be at 

most 1.62 x 10-7. Given that the use patterns are similar, differences between risk estimates for 

the two formulations were driven by the unit exposures for the various handler scenarios. The 

non-cancer inhalation MOE for Enable® 2F was ≥ 2,600 assuming baseline PPE, and the 

estimated combined dermal and inhalation cancer risk was at most 3.0 x 10-7. 

Occupational Post-Application Assessments

In the previous assessment, HED did not quantitatively assess non-cancer post-application 

dermal exposure and risk for Indar® 75 WSP or Enable® 2F due to the lack of systemic toxicity 

via the dermal route. Cancer risk for dermal post-application exposure was estimated to be at 

most 9.9 x 10-8. Since the use pattern has not changed, HED did not conduct an updated postapplication exposure assessment. A new assessment would address the following changes in the 

assumptions used: 1) increased body weight, from 70 to 80 kg; 2) increased life expectancy, 

from 70 to 78 years; and 3) increased transfer coefficient, from 1,000 to 1,900 cm2/hour for high 
Fenbuconazole Human Health Risk Assessment DP No. D403041 

Page 29 of 43

exposure activities. The use of these assumptions would increase estimated post-application 

cancer risk to approximately 1.4 x 10-7. 

10.0 References

Fenbuconzole. Occupational Exposure Assessment to Support Use of a New Formulation on 

Peppers. D404874, C. Swartz, 1/31/13. 

Fenbuconazole: Acute, Chronic and Cancer Aggregate Dietary (Food and Drinking Water) 

Exposure Analysis for the Section 3 Registration Action Increasing the Tolerance for Peppers. 

D403621, D. McNeilly, 1/8/2013. 

Fenbuconazole. Petition for an Increased Tolerance and the Registration of an SC formulation 

Use on Peppers: Summary of Analytical Chemistry and Residue Data. D403621, D. McNeilly, 

12/8/2012. 

 

Fenbuconazole: Bridging Residue Data on Pepper from Indar® 75WSP to Enable® 2F 

Formulation. D390352, S. Oonnithan, 9/8/2011. 

Fenbuconazole: Human Health Risk Assessment for the Proposed Use on Peppers. D344351, 

D. Dotson, 6/12/2008. 

Fenbuconazole: Summary of Hazard and Science Policy Council (HASPOC) Meeting of 

December 20, 2012: Recommendation on the need for a 28-day inhalation study and 

acute/subchronic neurotoxicity studies in the rat (TXR # 0056540). 

Fenbuconazole. Petition for Registration for Use on Pepper, Bushberry Subgroup (13-B), and 

Cranberry. Summary of Analytical Chemistry and Residue Data, D313752, D. Dotson, 

6/12/2008. 

Occupational and Residential Exposure Assessment for Section 3 Registration for use of 

Fenbuconazole on Peppers, D345898, S. Wang, 5/28/2008. 

Fenbuconazole. Acute, Chronic, and Cancer Aggregate Dietary (Food and Drinking Water) 

Exposure Analysis for the Section 3 Registration Action, D350321, D. Dotson, 6/12/2008. 

Drinking Water Exposure Assessment for Fenbuconazole Use on Pepper, D344352, J. Lin, 

1/16/2008. 

Screening Level Estimates of Agricultural Uses (SLUA) for the Fungicide Fenbuconazole 

(129011), Sepehr Haddad, 11/13/2012. 

Fenbuconazole: Human Health Risk Assessment for Proposed Uses on Almonds, Apples, 

Bananas, Bushberries, Citrus Fruit, Cranberries, Grapes, Peanuts, Pecans, Stone Fruits, Sugar 

Beets, and Wheat. PC Code: 129011, DP Barcode: D316607, M. Collantes, et al, 8/3/2006. 
Fenbuconazole Human Health Risk Assessment DP No. D403041 

Page 30 of 43

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

to Address The Amended Propiconazole Section 3 Registration to Add Foliar Use on Sugarcane. 

T. Morton. D403618. 8/1/2012.

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

The Amended Propiconazole Section 3 Registration to Add Use on Sugarcane. T. Morton. 

D403619. 8/1/2012. 
Fenbuconazole Human Health Risk Assessment DP No. D403041 

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Appendix A. International Residue Limits 

Fenbuconazole (129011; 10/10/2012) 

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition: 

US Canada Mexico2 Codex3 

40 CFR § 180.480 

Plant/Livestock: combined residues of the 

fungicide fenbuconazole, alpha-[2-(4-

chlorophenyl)- ethyl]-alpha-phenyl-3-(1H1,2,4-triazole)- 1-propanenitrile, and its 

metabolites RH-9129, cis-5-(4-

chlorophenyl)- dihydro-3-phenyl-3-(1H1,2,4- triazole-1-ylmethyl)-2-3 H-furanone, 

and RH-9130, trans-5-(4- 

chlorophenyl)dihydro-3-phenyl-3- (1H-1,2,4-

triazole-1-ylmethyl)-2-3 H- furanone, 

expressed as fenbuconazole 

α-[2-(4-chlorophenyl)ethyl]-αphenyl-1H-1,2,4- 

triazole-1-propanenitrile, including 

the metabolites 

cis-5-(4-chlorophenyl)-dihydro-3-

phenyl-3-(1H-1,2,4- 

triazol-1-ylmethyl)-2-3H-furanone 

and trans-5-(4- 

chlorophenyl)-dihydro-3-phenyl-3-

(1H-1,2,4- 

triazol-1-ylmethyl)-2-3H-furanone 

 Fenbuconazole. The 

residue is fat-soluble. 

Commodity1 Tolerance (ppm) /Maximum Residue Limit (mg/kg) 

US Canada Mexico2 Codex3

Pepper 1.0 

 0.6 peppers 

2 peppers Chili, dried 

 (draft MRL awaiting 

ARfD evaluation)

 

Completed: M. Negussie; 10/12/2012 

1

 Includes only commodities of interest for this action. Tolerance values should be the HED recommendations and not those proposed by the 

applicant.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. 

Appendix B. Toxicology Profile 

B.1 Toxicology Data Requirements

The requirements (40 CFR 158.340) for food uses of fenbuconazole are in Table B1. Use of the 

new guideline numbers does not imply that the new (1998) guideline protocols were used. The 

acute and chronic toxicity profiles are shown in Tables B.2.1 and B.2.2, respectively. 
Fenbuconazole Human Health Risk Assessment DP No. D403041 

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Study 

Technical

Required Satisfied

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

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

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

870.2400 Acute Eye Irritation ....................................................... 

870.2500 Acute Dermal Irritation ................................................. 

870.2600 Skin Sensitization .......................................................... 

yes 

yes 

yes 

yes 

yes 

yes 

yes 

yes 

yes 

yes 

yes 

yes 

870.3100 90-Day Oral Toxicity in Rodents .................................. 

870.3150 90-Day Oral Toxicity in Nonrodents ............................. 

870.3200 21/28-Day Dermal Toxicity ........................................... 

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

870.3465 28/90-Day Inhalation Toxicity ...................................... 

yes 

yes 

yes 

no 

no 

yes 

yes 

yes 

- 

- 

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

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

870.3800 Reproduction and Fertility Effects ................................. 

yes 

yes 

yes 

yes 

yes 

yes 

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

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

870.4200a Carcinogenicity (rat) ...................................................... 

870.4200b Carcinogenicity (mouse) ................................................ 

870.4300 Combined Chronic Toxicity/Carcinogenicity ................ 

yes 

yes 

yes 

yes 

yes 

yes 

yes 

yes 

yes 

yes 

870.5100 Mutagenicity—Bacterial Reverse Mutation Test .......... 

870.5300 Mutagenicity—Mammalian Cell Gene Mutation Test .. 

870.5385 Mutagenicity—Structural Chromosomal Aberrations ... 

870.5550 Mutagenicity—Other Genotoxic Effects ....................... 

yes 

yes 

yes 

yes 

yes 

yes 

yes 

yes 

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

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

870.6300 Developmental Neurotoxicity ........................................ 

no 

no 

no 

- 

- 

- 

870.7485 Metabolism and Pharmacokinetics ................................ 

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

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

yes 

yes 

yes 

yes 

yes 

no 
Fenbuconazole Human Health Risk Assessment DP No. D403041 

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B.2 Toxicity Profiles

Table B.2.1 - Acute Toxicity of Fenbuconazole - Technical (shaded) and End-Use (2F, 24% ai) Product

Guideline 

No. Study Type MRID Results Toxicity Category

870.1100 Acute Oral - Rats 41031209 Oral LD50 (M) > 2000 mg/kg III 

870.1100 Acute Oral - Rats 41031207 Oral LD50 (M and F) > 2000 mg/kg III 

870.1100 Acute Oral - Rats 41031221 Oral LD50 (M) > 5000 mg/kg IV 

870.1100 Acute Oral - Rats 41031222 Oral LD50 (F) > 5000 mg/kg IV 

870.1200 Acute Dermal - Rats 41031208 LD50 (M and F) > 5000 mg/kg IV 

870.1200 Acute Dermal - Rats 41031223 LD50 (M) > 5000 mg/kg IV 

870.1200 Acute Dermal - Rats 41031224 LD50 (F) > 5000 mg/kg IV 

870.1300 Acute Inhalation - Rats 41398201 

LC50 (M and F) > 2.1 mg/L 

Particle size too large. Requirement 

was waived because of a problem in 

generating respirable dust particles 

or liquid aerosol. 

III 

870.1300 Acute Inhalation - Rats 41031225 LC50 (M and F) > 2.1 mg/L III 

870.2400 Primary Eye IrritationRabbits 41031211 Not irritating to unwashed eyes IV 

870.2400 Primary Eye IrritationRabbits 41031226 Not irritating to the eyes IV 

870.2500 Primary Dermal 

Irritation- Rabbits 41031212 Not irritating to the skin IV 

870.2500 Primary Dermal 

Irritation- Rabbits 41031227 Not irritating to the skin IV 

870.2600 Dermal SensitizationGuinea pigs 41031213 Is not a sensitizer under conditions 

of study. N/A 

870.2600 Dermal SensitizationGuinea pigs 41031228 Is not a sensitizer under conditions 

of study. N/A 

Table B.2.2 - Toxicity Profile of Fenbuconazole Technical

Guideline 

No.

Study Type MRID Doses Results
Fenbuconazole Human Health Risk Assessment DP No. D403041 

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Table B.2.2 - Toxicity Profile of Fenbuconazole Technical

Guideline 

No.

Study Type MRID Doses Results

870.3100 90-Day oral 

toxicity rodents - 

rats 

41073502 0, 20, 80, 400 or 1600 ppm 

(Males: 0, 1.3, 5.1, 25.3 or 

103.0 mg/kg/day; 

Females: 0, 1.5, 6.3, 31.1 

or 123.9 mg/kg/day) 

NOAEL = 5.1/6.3 mg/kg/day 

(M/F) 

LOAEL = 25.3/31.1 mg/kg/day 

(M/F) based on decreased body 

weight, liver effects 

(histopathology, clinical 

chemistry effects and increased 

liver weight) 

870.3100 90-Day oral 

toxicity rodents - 

mice 

41073503 0, 20, 60, 180, and 540 ppm 

(Males: 0, 3.8, 11.1, 28.6 or 

99.1 mg/kg/day; 

Females: 0, 5.7, 17.6, 50.4 

or 139.2 mg/kg/day) 

NOAEL = 11.1/17.6 mg/kg/day 

(M/F) 

LOAEL = 28.6/50.4 mg/kg/day 

(M/F) based on liver 

histopathology and clinical 

chemistry changes 

870.3150 90-Day oral 

toxicity in 

nonrodents - 

dogs 

41073504 0, 30, 100, 400, and 1600 

ppm 

(Males: 0, 1.0, 3.3, 13.3 or 

50.4 mg/kg/day; 

Females: 0, 1.1, 3.5, 14.0 

or 53.3 mg/kg/day) 

NOAEL = 13.3/14.0 mg/kg/day 

(M/F) 

LOAEL = 50.4/53/3 mg/kg/day 

(M/F) based on liver 

histopathology, clinical chemistry 

in females 

870.3200 21/28-Day 

dermal toxicity - 

rats 

41875013 

42882701 

0, 250, 625 or 1000 

mg/kg/day 

NOAEL = 1000 mg/kg/day 

(HDT) (systemic and local dermal 

irritation) 

LOAEL = >1000 mg/kg/day 

(systemic and local dermal 

irritation) 

870.3250 90-Day dermal 

toxicity 

N/A N/A Not performed 

870.3465 28 or 90-Day 

inhalation 

toxicity 

N/A N/A Not performed 

870.3700 Prenatal 

developmental in 

rodents - rats 

41031214 

41073505 

0, 30, 75 or 150 mg/kg/day Maternal NOAEL = 30 

mg/kg/day 

Maternal LOAEL = 75 

mg/kg/day based on decreased 

body weight and body weight 

gain 

Developmental NOAEL = 30 

mg/kg/day 

Developmental LOAEL = 75 

mg/kg/day 

based on decreased implantations, 

increased post-implantation loss 

and a decrease in the number of 

live fetuses/dam 
Fenbuconazole Human Health Risk Assessment DP No. D403041 

Page 35 of 43

Table B.2.2 - Toxicity Profile of Fenbuconazole Technical

Guideline 

No.

Study Type MRID Doses Results

870.3700 Prenatal 

developmental in 

nonrodents - 

rabbits 

41875014 

42882701 

0, 10, 30 or 60 mg/kg/day Maternal NOAEL = 10 

mg/kg/day 

Maternal LOAEL = 30 

mg/kg/day based on decreased 

food consumption and increased 

incidence of clinical signs 

(soft/scant/no feces and red 

discharge) 

Developmental NOAEL = 30 

mg/kg/day 

Developmental LOAEL = 60 

mg/kg/day 

based on increased early 

resorptions 

870.3700 Prenatal 

developmental in 

nonrodents - 

rabbits 

 

45259401 

0, 15 or 45 mg/kg/day Maternal NOAEL = 15 

mg/kg/day 

Maternal LOAEL = 45 

mg/kg/day, based on decreased 

food consumption and increased 

incidence of clinical signs 

(soft/scant/no feces) 

Developmental NOAEL = 15 

mg/kg/day 

Developmental LOAEL = 45 

mg/kg/day based on decreased 

fetal body weight
Fenbuconazole Human Health Risk Assessment DP No. D403041 

Page 36 of 43

Table B.2.2 - Toxicity Profile of Fenbuconazole Technical

Guideline 

No.

Study Type MRID Doses Results

870.3800 Reproduction 

and fertility 

effects - rats 

41875015 0, 8, 80 or 800 ppm (0, 0.4, 

4 or 40 mg/kg/day) 

Parental systemic NOAEL = 4 

mg/kg/day 

Parental systemic LOAEL = 40 

mg/kg/day 

based on maternal death during 

delivery, decreased body weight 

and food consumption, increased 

number of dams not delivering 

viable or delivering nonviable 

offspring, and increased adrenal 

and thyroid/parathyroid weights 

Reproductive NOAEL = 40 

mg/kg/day (HDT) 

Reproductive LOAEL = >40 

mg/kg/day 

Offspring systemic NOAEL = 4 

Offspring systemic LOAEL = 

40 mg/kg/day 

based on decreased mean pup 

body weight, increased number of 

stillborn pups, decreased number 

of total offspring delivered, and 

decreased viability index 

870.4100 Chronic toxicity 

- rodents 

 See 870.4300 

870.4100 Chronic toxicity 

- dogs 

41875049 0, 15, 150 or 1200 ppm (0, 

0.38, 3.75 or 30 mg/kg/day) 

NOAEL = 3.75/0.38 mg/kg/day 

(M/F) 

LOAEL = 30/3.75 mg/kg/day 

(M/F) based on decreased body 

weight gain 

Note: dose-related adaptive liver 

changes were observed in highdose males and females. 

870.4200 Carcinogenicity - 

rats 

 See 870.4300 

870.4200 Carcinogenicity - 

mice 

41893301 

41635303 

Males: 0, 10, 200 or 650 

ppm (0, 1.43, 28.6 or 92.9 

mg/kg/day) 

Females: 0, 10, 650 or 

1300 ppm (0, 1.43, 92.9 or 

186 mg/kg/day) 

NOAEL = 1.43 mg/kg/day (M & 

F) 

LOAEL = 28.6/92.9 mg/kg/day 

(M/F) based on decreased body 

weight, increased relative and 

absolute liver weight, and 

hepatocellular hypertrophy and 

vacuolization

Evidence of carcinogenicity
Fenbuconazole Human Health Risk Assessment DP No. D403041 

Page 37 of 43

Table B.2.2 - Toxicity Profile of Fenbuconazole Technical

Guideline 

No.

Study Type MRID Doses Results

870.4300 Combined 

chronic toxicity/ 

carcinogenicity - 

rat 

41635301 

41635302 

Control - 0 ppm 

Low - 4 ppm (weeks 1 & 2), 

6 ppm (weeks 3 & 4) or 8 

ppm (weeks 5-term) 

Mid - 40 ppm (weeks 1 & 

2), 60 ppm (weeks 3 & 4) or 

80 ppm (weeks 5-term) 

High - 400 ppm (weeks 1 & 

2), 600 ppm (weeks 3 & 4) 

or 800 ppm (weeks 5-term) 

(Males: 0, 0.31, 3.03 or 

30.62 mg/kg/day; 

Females: 0, 0.4, 4.02 or 

43.07 mg/kg/day) 

NOAEL = 3.0/4.0 mg/kg/day 

(M/F) 

LOAEL = 30.6/43.1 mg/kg/day 

(M/F) based on decreased body 

weight gain (F), hepatocellular 

enlargement and vacuolization 

(F), increased thyroid weight 

(M&F), and histopathological 

lesions in the thyroid gland (M) 

Evidence of carcinogenicity

870.4300 Combined 

chronic toxicity/ 

carcinogenicity - 

rat 

42021901 

42055001 

Control - 0 ppm 

Low - 400 ppm (weeks 1 & 

2), 600 ppm (weeks 3 & 4) 

or 800 ppm (weeks 5-term) 

High - 800 ppm (weeks 1 & 

2), 1200 ppm (weeks 3 & 4) 

or 1600 ppm (weeks 5-term) 

(0, 30.4, and 63.9 

mg/kg/day) 

NOAEL = Not established 

LOAEL = 30.4 mg/kg/day (M) 

based on decreased body weight 

gain, increased liver weight, and 

increased thyroid and parathyroid 

weights 

Note: only males were used in 

this study. 

Insufficient evidence of 

carcinogenicity

870.5100 Gene mutation - 

bacterial reverse 

mutation assay 

41031216 TA1535 - 30-300 ug 

TA1537 - 30-300 ug 

TA98 - 0.2-20 ug 

TA100 - 160-1600 ug 

No mutagenic activity in bacteria 

(Salmonella typhimurium) under 

conditions of this assay. 

Note: only TA1535, TA1537, 

TA98, and TA100 were tested. 

This study is classified 

unacceptable. 

870.5100 Gene mutation - 

bacterial reverse 

mutation assay 

41031217 TA1535 - 30-300 ug 

TA1537 - 30-300 ug 

TA98 - 30-300 ug 

TA100 - 30-300 ug 

No mutagenic activity in bacteria 

(Salmonella typhimurium) under 

conditions of this assay. 

Note: only TA1535, TA1537, 

TA98, and TA100 were tested. 

This study is classified 

unacceptable. 
Fenbuconazole Human Health Risk Assessment DP No. D403041 

Page 38 of 43

Table B.2.2 - Toxicity Profile of Fenbuconazole Technical

Guideline 

No.

Study Type MRID Doses Results

870.5300 Cytogenetics - in 

vitro mammalian 

cell gene 

mutation test 

(CHO Cells) 

41031218 15-50 μg/mL without S9 

activation 

35-60 μg/mL with S9 

activation 

No increase in mutant frequency 

at the HGPRT locus, in the 

presence or absence of S9 

activation. 

870.5385 Cytogenetics - 

mammalian bone 

marrow 

chromosomal 

aberration test 

(rats) 

41031219 0, 0.25, 1.25 or 2.5 g/kg No increase in number of cells 

with aberrations or in aberrations 

per cell. 

870.5550 Other effects - 

unscheduled 

DNA synthesis 

in mammalian 

cells in culture 

(rats) 

41031220 0, 7.5, 10.0, 12.5 or 15.0 

μg/mL 

No evidence (or a dose-related 

positive response) that 

unscheduled DNA synthesis was 

induced. 
Fenbuconazole Human Health Risk Assessment DP No. D403041 

Page 39 of 43

Table B.2.2 - Toxicity Profile of Fenbuconazole Technical

Guideline 

No.

Study Type MRID Doses Results

870.7485 Metabolism and 

pharmacokinetics 

- rat 

41875017 

41875018 

1) 1 mg/kg radiolabelled, 

single dose by oral gavage 

2) 100 mg/kg radiolabelled, 

single dose by oral gavage 

3) 1 mg/kg unlabelled, 14 

days in the diet, PLUS 1 

mg/kg radiolabelled, single 

dose by oral gavage 

4) 1 mg/kg radiolabelled, by 

i.v. injection 

The mean recovery of 

radioactivity 4 days after exposure 

was 82.6-93.0% following single 

or repeated oral doses and 88.2-

99.2% following single i.v. doses, 

indicating rapid absorption, 

distribution, and elimination. 

Rapid elimination and low tissue 

levels indicate low 

bioaccumulation of the parent and 

metabolites. 

Elimination occurred primarily by 

biliary excretion because recovery 

of radioactivity was mostly in the 

feces: 75.6-83.7% following oral 

exposure and 77.2-91.4% 

following i.v. exposure. In urine, 

radioactivity recovery was 5.5-

12.6% for all dose scenarios. 

Peak radioactivity in the blood 

occurred 3 hours following a 

single low dose and 3-6 hours 

after a single high dose, indicating 

biphasic elimination. 

Only 8.5-14.8% and 0.0-2.7% of 

the parent compound was 

recovered in the feces and urine, 

respectively, indicating extensive 

metabolism. A number of major 

metabolites were identified; 

however, 50% and 20% of 

metabolites in the feces and urine, 

respectively, were not identified. 

Sex-related differences include a 

greater number of sulfate 

metabolites in female excreta 

compared to males, and a greater 

number of ketoacid metabolites in 

male urine compared to female 

urine. 
Fenbuconazole Human Health Risk Assessment DP No. D403041 

Page 40 of 43

Table B.2.2 - Toxicity Profile of Fenbuconazole Technical

Guideline 

No.

Study Type MRID Doses Results

870.7485 Metabolism and 

pharmacokinetics 

- rat 

42900801 1) 1 mg/kg radiolabelled, 

single dose by oral gavage 

2) 100 mg/kg radiolabelled, 

single dose by oral gavage 

3) 1 mg/kg unlabelled, 14 

days in the diet, PLUS 1 

mg/kg radiolabeled, single 

dose by oral gavage 

The mean recovery of 

radioactivity 3-4 days after 

exposure was 90.4-104.5% 

following single or repeated oral 

doses, indicating rapid absorption, 

distribution, and elimination. 

Bioaccumulation of the parent 

compound and metabolites is low. 

There were no major sex- or doserelated differences in absorption, 

distribution, or elimination. 

Elimination occurred primarily by 

biliary excretion: recovery of the 

administered dose occurred 

mainly in the bile (79.1-87.1%) 3 

days after exposure and mostly in 

the feces (78.7-94.4%) 4 days 

after exposure. In contrast, 

radioactivity recovery in the urine 

was 3.2-11.5% at 3 and 4 days 

after exposure. 

Extensive metabolism occurred; 

numerous metabolites were found 

in the feces and urine. There is a 

dose-related difference in 

metabolism. A higher amount of 

parent compound was found in 

the feces following the single high 

dose compared to the single or 

repeated low dose(s), which 

suggests that saturation might be 

occurring at the high dose. 

870.7485 Metabolism and 

pharmacokinetics 

– rat 

(supplemental) 

46473401 1) 1 mg/kg radiolabelled, 

single dose by oral gavage, 

urine and feces collection up 

to 48 hrs; 

2) 100 mg/kg radiolabelled, 

single dose by oral gavage, 

urine and feces collection up 

to 72 hrs; 

3) 100 mg/kg radiolabelled 

single dose by oral gavage, 

urine and feces collection 

72-96 hrs.

Evaluation of 1,2,4-triazole levels 

in urine and feces occurred at very 

low levels (2.48% AD, males and 

1.0% AD, females). Alanine and 

acetic acid conjugates were not 

detected. 
Fenbuconazole Human Health Risk Assessment DP No. D403041 

Page 41 of 43

Table B.2.2 - Toxicity Profile of Fenbuconazole Technical

Guideline 

No.

Study Type MRID Doses Results

870.7600 Dermal 

penetration - rat 

41875019 0, 0.125, 1.25 or 12.5 mg/kg 

Note: End-use product 

(23.1%) was tested 

Mean % of the dose absorbed 

(sum of urine, feces, carcass, and 

skin) after 10 hrs of exposure: 

0.125 mg/kg: 4.25% 

1.25 mg/kg: 2.08% 

12.5 mg/kg: 0.45% 
Fenbuconazole Human Health Risk Assessment DP No. D403041 

Page 42 of 43

Appendix C. Physical/Chemical Properties 

Table C.1. Physical and Chemical Properties of the Technical Grade Fenbuconazole

Parameter Value Reference 

Molecular weight 353.8 

D310959, S. 

Oonnithan, 

7/25/2008 

 

Melting point 126.5–127.0°C 

pH Not available 

Bulk Density 0.50 g/mL 

Water solubility at 22°C 3.8 mg/L 

Solvent solubility (g/L) at 25°C Acetonitrile 231 

Cyclohexanone 445 

Ethyl alcohol 39 

1-octanol 13 

Aromatic 200 77 

Ethyl acetate 159 

Heptane 1.0 

Vapor pressure at 25°C (PAI) 0.37 ×10-7 mm Hg (4.9 × 10-6 Pa) 

Dissociation constant (pKa) (PAI) Not expected to dissociate in water 

Octanol/water partition coefficient 

Log(KOW) 

Log(KOW) = 3.22 

UV/visible absorption spectrum λ max (nm)

196 

262 

268 

275 

ε (L·mol-1·cm-1)

53,000 

750 

740 

480 

Soil Half-life (t1/2 in days) Aerobic: 285 and 367 days, silty clay loam 

and sandy loam soils, respectively 

Anaerobic: 451 and 655 days, silty clay loam 

and sandy loam soils, respectively 

D344352, J. Lin, 

1/16/08 
Fenbuconazole Human Health Risk Assessment DP No. D403041 

Page 43 of 43

Appendix D. Review of Human Research 

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

intentionally exposed to a pesticide or other chemical. These studies, listed below, have been 

reviewed for ethical conduct. The studies were considered appropriate for use in risk 

assessments. 

The PHED Task Force, 1995. The Pesticide Handlers Exposure Database, Version 

1.1. Task Force members Health Canada, U.S. Environmental Protection Agency, and 

the National Agricultural Chemicals Association, released February, 1995. 

The Agricultural Handler Exposure Task Force (AHETF), 2011. The Occupational 

Handler Unit Exposure Surrogate Reference Table. U.S. Environmental Protection 

Agency. Released June 21, 2011.