Fenazaquin Human Health Risk Assessment DP No. D391819 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

Date: August 29, 20 14 

OFFICE OF 

CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

SUBJECT: Fenazaquin: Human Health Risk Assessment for Proposed New Uses on 

Almonds and Cherries. 

PC Code: 04450 I 

Decision No.: 444200 

Petition No.: I F7825 

Risk Assessment Type: Single Chemical/Aggregate 

TXR No.: NA 

MRID No.: NA 

DP Barcode: 03918 19 

Registration Nos.: 10163-295; 10 163-GEE 

Regulatory Action: Section 3Registration 

Case No.: NA 

CAS No.: 120928-09-8 

40 CFR: 180.632 

FROM: Cassi Walls, Ph.D., Senior Biologist ~ 7-~ 

Vincent Chen, Toxicologist ~, _ v;' z:- _ Stephen Funk, Senior Scien~~ (_ _ Kristin Rury, Biologist ~ ~-

Risk Assessment Branch III 

Health Effects Division (7509P) 

THROUGH: Christine Olinger, Branch Chief /} / / _,// , 

Health 

Risk Asse

Effect

ssm

s 

e

Divis

nt Branch 

ion (7509P) 

III (_}I/ f c/-~ 

TO: Olga Odiott, Risk Manager 

Insecticide and Rodenticide Branch 

Registration Division (7505P) 

The Health Effects Division (HED) of the Office of Pesticide Programs (OPP) is charged with 

estimating the risk to human health from exposure to pesticides. Gowan Company, LLC 

(Gowan) has requested a registration of new uses of fenazaquin on almonds and cherries. The 

Registration Division (RD) of OPP has requested that HED evaluate hazard and exposure data 

and conduct dietary, occupational, residential, and aggregate exposure assessments, as needed, to 

estimate the risk to human health that will result from the proposed uses of fenazaquin. A 

summary of the findings and an assessment of human health risk resulting from the proposed 

uses of fenazaquin on almonds and cherries are provided in this document. The HED team 

members contributing to this risk assessment include Cassi Walls (risk assessment and dietary 

risk assessment), Vincent Chen (hazard reevaluation), Steve Funk (residue chemistry), and 

Kristin Rury (occupational/residential assessments). 

Page 1of45 
Fenazaquin Human Health Risk Assessment DP No. 0391819 

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

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

2.1 Data Deficiencies ........................ .................................. .... .... .... ........ .............................. 7 

2.2 Tolerance Considerations ................................................................ ........ .... .... ........ ...... 7 

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

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

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

2.2.4 International Harmonization ....................................... ........ .... ............ .... ............ .... .. 8 

2.3 Label Recommendations ........... .... .... ........ ............ ......................................................... 8 

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 ............. .... .... .... .... .... ............................... .... .... ......... .. 9 

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

4.0 Hazard Characterization and Dose-Response Assessment.. ........................................ 10 

5.0 Dietary Exposure and Risk Assessment ........ .... .... .... .... .... ............ ... .. ... .... ........ ........ ..... 17 

5.1 Metabolite/Degradate Residue Profile .......................... ........ ................ ........... ..... ..... 17 

5.1.1 Summary of Plant and Animal Metabolism Studies ............................................. 17 

5.1.2 Summary of Environmental Degradation .............................................................. 18 

5.1.3 Comparison of Metabolic Pathways .......... ....................... .................... .... .... ..... .... . 18 

5.1.4 Residues of Concern Summary and Rationale ...................................................... 19 

5.2 Food Residue Profile .......................................................... ........... ............. ........ .... .... .. 20 

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

5.4 Dietary Risk Assessment .................................... ........................ ... .... ......... .... ......... ..... 21 

5.4.1 Description of Residue Data Used in Dietary Assessment ...................... .............. 21 

5.4.2 Percent Crop Treated Used in Dietary Assessment .............................................. 21 

5.4.3 Acute Dietary Risk Assessment ..... .... ....................................................... .... ......... .. 21 

5.4.4 Chronic Dietary Risk Assessment ............ ........ .... .... ... ............................................ 22 

5.4.5 Cancer Dietary Risk Assessment.. ............................................... .... .... .................... 22 

5.4.6 Summary Table ..... ........................................................................ .... ......... ........ ....... 22 

6.0 Residential (Non-Occupational) Exposure/Risk Characterization ...................... .... ... 23 

6.1 Residential Handler Exposure .................. .... .... .... ........... .... .... .... .... ........................... 23 

6.2 Post-Application Exposure ................................................... ........ ................ ... ............ 23 

6.3 Residential Risk Estimates for Use in Aggregate Assessment.. ..... ....... ............. ....... 23 

6.4 Residential Bystander Post-application Inhalation Exposure .......................... .... ... 24 

6.5 Spray Drift ................ ....... .................................................. ............ .... .... ... .................... 24 

7.0 Aggregate Exposure/Risk Characterization .... ....................................... .... .... .... .... .... ... 24 

7.1 Acute Aggregate Risk ...... .......................................... .... .... ........................................... 24 

7.2 Short-Term Aggregate Risk .. .... .... ... .................................................................... ....... 25 

7.3 Chronic Aggregate Risk ............................... ............................................................... 25 

7.4 Cancer Aggregate Risk .......... ...................................................... .... .... .... .... ................ 25 

8.0 Cumulative Exposure/Risk Characterization ....................................................... ........ 25 

9.0 Occupational Exposure/Risk Characterization ............................................................ 26 

9.1 Short-Term Handler Risk ............................................................... .... .... .................... 26 

9.2 Short-/lntermediate-Term Post-Application Risk ............................... ..................... 28 

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Fenazaquin Human Health Risk Assessment DP No. D391819

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9.2.1 Dermal Post-application Risk.................................................................................. 28

9.2.2 Inhalation Post-application Risk............................................................................. 28

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

Appendix A. Toxicology Profile................................................................................................ 30

A.1 Toxicology Data Requirements................................................................................... 30

Appendix B. Proposed Metabolic Pathways for Fenazaquin (EL-436) in the Rat ............... 35

Appendix C. Physical/Chemical Properties............................................................................. 36

Appendix D. Structure of Fenazaquin and its major metabolites/degradates..................... 37
Fenazaquin Human Health Risk Assessment DP No. D391819

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1.0 Executive Summary

Use Profile: 

Fenazaquin is a quinazoline-derived insecticide used to control mites and whiteflies, currently 

registered as an emulsifiable concentrate (EC) for use on outdoor ornamental plants, ornamental 

plants inside greenhouses, Christmas tree plantations, and non-bearing fruit and nut trees. There 

are also existing tolerances for fenazaquin on imported apples, citrus (except grapefruit), citrus 

oil, and pears. 

The Registrant, Gowan Company, has proposed domestic uses of fenazaquin on cherries and 

almonds. The proposed uses will be added to the formulated end use product label (GWN-1708 

F, 18.79% fenazaquin, EPA Reg. No. 10163-GEE), which is a liquid formulation containing 

18.79% fenazaquin by weight and 1.6 lbs active ingredient (ai) per gallon. The product is a 

foliar spray applied using aerial and ground equipment at a maximum single and seasonal 

application rate of 0.45 lb ai/A. 

Hazard Identification:

The most consistently observed effects of fenazaquin exposure across species, sexes, and 

treatment durations were decreases in body weight, food consumption, and food efficiency. 

Fenazaquin was not observed to target a specific tissue. Fenazaquin is classified as “Not likely to 

be Carcinogenic to Humans.” There was no observed toxicity with respect to developmental 

toxicity, reproductive toxicity, neurotoxicity, mutagenicity, genotoxicity, or immunotoxicity. 

Based on the available data, toxicity endpoints and points of departure (PODs) have been 

selected for acute and chronic dietary, short-term incidental oral, and short- and intermediateterm inhalation exposure scenarios. A dermal assessment is not required for this chemical 

because there was no observed systemic toxicity in rats treated up to the limit dose (1000 

mg/kg/day) and no developmental toxicity, reproductive toxicity, neurotoxicity, and

immunotoxicity effects were observed in the database. The Food Quality Protection Act (FQPA) 

Safety Factor has been reduced to 1x because the toxicity database is complete, there is no 

concern for susceptibility in infants and young children, there are no neurotoxicity concerns, and 

there are no residual uncertainties regarding exposure.

Dietary Exposure (Food/Water):

Acute: An unrefined acute dietary (food and drinking water) assessment was conducted. The 

assumptions of this dietary assessment included tolerance level residues for all registered and 

proposed crops and 100% crop treated (CT). Default processing factors were used. The surface

water estimated drinking water concentration (EDWC) of 5.74 μg/L from the Tier II PRZM 

(Pesticide Root Zone Model) and EXAMS (EXposure Analysis Modeling System) modeling was 

incorporated directly into the dietary assessment.

The acute dietary (food and drinking water) exposure to fenazaquin is below HED’s level of 

concern [i.e., <100% of the acute Population Adjusted Dose (aPAD)] for the general U.S. 

population and all population subgroups. The acute dietary exposure estimates at the 95th

percentile are 3% of the aPAD for the general U.S. population and 10% of the aPAD for children 

1-2 years old, the most highly exposed population subgroup. 
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Chronic: An unrefined chronic dietary (food and drinking water) assessment was conducted. 

The assumptions of this dietary assessment included tolerance level residues for all registered 

and proposed crops and 100% crop treated (CT). Default processing factors were used. The 

surface water EDWC of 2.09 μg/L from the Tier II PRZM-EXAMS modeling was incorporated 

directly into the dietary assessment.

The chronic dietary (food and drinking water) exposure to fenazaquin is below HED’s level of 

concern [i.e., <100% of the chronic Population Adjusted Dose (cPAD)] for the general U.S. 

population and all population subgroups. The chronic dietary exposure estimates are 2% of the 

cPAD for the general U.S. population and 10% of the cPAD for children 1-2 years old, the most 

highly exposed population subgroup. 

Residential Exposure:

There are no residential uses being requested at this time. However, the existing residential

ornamental use was reassessed to incorporate revisions to the Residential Standard Operating 

Procedures (SOPs) and body weight assumptions. 

Handler Exposures:

There are no residential handler risk estimates of concern for the existing uses of fenazaquin 

using the Revised Residential SOPs. The level of concern (LOC) for residential handler risk 

estimates is a margin of exposure (MOE) of 100 (i.e., MOE < 100 are of concern). Short-term 

inhalation MOEs for residential handlers range from 190,000 to 19,000,000. 

Post-application Exposures:

A quantitative residential post-application assessment was not conducted for fenazaquin 

exposure for adults and children because: (1) dermal endpoints for were not selected; (2) postapplication inhalation exposure is considered negligible from use on ornamentals; and (3) there 

is no incidental oral exposure expected from fenazaquin use on ornamental plants. 

Aggregate Exposure:

Acute: Aggregate acute risk is equivalent to acute dietary risk (e.g., food and drinking water

exposure) where the estimates are not of concern.

Chronic: Aggregate chronic risk is equivalent to chronic dietary risk (e.g., food and drinking 

water exposure) where the estimates are not of concern.

Short- and Intermediate Term: There is potential short-term aggregate exposure to fenazaquin

for adults from dietary exposure (which is considered background exposure) and residential 

dermal and inhalation exposures from handling fenazaquin. However, since no hazard was 

identified for the dermal route of exposure, short-term aggregate risk estimate included dietary 

and inhalation exposures only. The aggregate MOE for adults is 5,200 and not of concern to 

HED. Since there is no residential exposure for children, there is no potential short-term 

aggregate risk.

Intermediate-term aggregate exposures are not expected based on the use profile of fenazaquin, 

therefore they were not assessed.
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Occupational Exposure:

Occupational Handler Exposures:

Occupational short- and intermediate- term dermal and inhalation exposures are expected from 

fenazaquin handler activities associated with the proposed almond and cherry uses. Since no 

hazard was identified for the dermal route of exposure, dermal exposures were not assessed. 

MOEs greater than 100 for the inhalation route is deemed adequate to protect occupational 

fenazaquin handlers. All handler scenarios resulted in MOEs greater than the level of concern 

(LOC = MOEs ≥ 100) for inhalation exposures and, therefore are not of concern. 

Occupational Post-application Exposures:

Occupational short-term dermal exposures are expected from fenazaquin post-application 

activities associated with the proposed almond and cherry uses. However, since no hazard was 

identified for the dermal route of exposure, dermal exposures were not quantitatively assessed. 

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

exposure assessment was not performed for fenazaquin at this time. If new policies or 

procedures are put into place, the Agency may revisit the need for a quantitative post-application 

inhalation exposure assessment for fenazaquin.

Restricted Entry Interval: The labeled restricted entry interval (REI) of 12-hrs is adequate to 

protect agricultural workers from post-application exposures to fenazaquin. Per the Worker 

Protection Standard (WPS), fenazaquin is classified as Toxicity Category III for acute inhalation

and IV for acute dermal exposure and requires a 12-hr REI. 

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 data, which include studies from 

the PHED, AHETF, and Residential SOPs (for the garden/tree SOP); are (1) subject to ethics 

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

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

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

use, can be found at http://www.epa.gov/pesticides/science/handler-exposure-data.html and 

http://www.epa.gov/pesticides/science/post-app-exposure-data.html.

Environmental Justice Considerations: 

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

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

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

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

2.0 HED Recommendations

HED has examined the residue chemistry, toxicity, and exposure databases for fenazaquin and 

concluded that, provided a revised Section F is submitted, there are no deficiencies that would 

preclude granting a Section 3 registration on almonds and cherries. 
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2.1 Data Deficiencies

None

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

An acceptable analytical method exists for the enforcement of plant commodity tolerances. The 

HPLC-MS/MS method is the same as that used for data collection and has been shown 

acceptable over a range of commodities. The method has undergone successful independent 

laboratory confirmation. Testing with radiolabeled samples showed that the method recovers 

adequate amounts of the analyte. 

2.2.2 Recommended Tolerances

Tolerances are established for residues of fenazaquin, including its metabolites and degradates, 

in or on the commodities in the table below. Compliance with the tolerance levels specified 

below for plant commodities is to be determined by measuring only fenazaquin in or on the 

commodity.

Table 2.2.2. Tolerance Summary for Fenazaquin

Commodity Established/Proposed 

Tolerance (ppm)

Recommended 

Tolerance (ppm)

Comments

Correct Commodity Definition

Almond, hulls 0.6 4.0 A revised Section F must be 

submitted to propose a tolerance at 

4.0 ppm

Almond 0.02 0.02 Almond

Cherry 1.5 2.0 A revised Section F must be 

submitted to propose a tolerance at 

2.0 ppm.

2.2.3 Revisions to Petitioned-For Tolerances

The use of the Organization of Economic Cooperation and Development (OECD) tolerance 

derivation procedures indicates the need for the following changes in proposed tolerances: 

cherries from 1.5 ppm to 2.0 ppm and almond hull from 0.6 ppm to 4.0 ppm. 

The tolerance expression (for plant commodities) should be stated as follows:

Tolerances are established for residues of the insecticide fenazaquin, 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 

fenazaquin, or 4-[2-[4-(1,1-dimethylethyl)phenyl]ethoxy]quinazoline.
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2.2.4 International Harmonization

There are no established maximum residue limits (MRLs) for fenazaquin in the Codex system. 

There are no established or pending MRLs in Canada for fenazaquin. Therefore, there are no 

harmonization issues.

2.3 Label Recommendations

Based on discussions with the Registrant and the proposed use pattern (foliar insecticide for use 

in orchards on almond and cherry trees), HED recommends that language regarding chemigation 

application be removed from the proposed label. Fenazaquin application via chemigation should 

also be restricted from on the proposed label. 

3.0 Introduction

Fenazaquin, 4-tert-butylphenethyl quinazolin-4-yl ether, is a quinazoline class 

insecticide/acaricide used to control mites and whiteflies. Fenazaquin is currently registered in 

the U.S. for use on Christmas trees (plantations), outdoor and greenhouse-grown ornamental 

plants, established ornamental landscapes (including interiorscapes and around residential 

premises), and on non-bearing fruit and nut trees. Additionally, fenazaquin has tolerances to 

support the importation of apples, pears and citrus fruits treated with fenazaquin that are grown 

in other countries for export to the U.S. 

3.1 Chemical Identity

The structure and nomenclature of fenazaquin is presented below in Table 3.1. The chemical 

structure of fenazaquin and its major metabolites/degradates are presented in Appendix D.

Table 3.1. Fenazaquin Nomenclature.

Compound

Common name Fenazaquin

Molecular weight 306.4

Company experimental names XDE-436, EL-436, XRD-562; DE-436

IUPAC name 4-tert-butylphenethyl quinazolin-4-yl ether

CAS name 4-[2-[4-(1,1-dimethylethyl)phenyl]ethoxy]quinazoline

CAS registry number 120928-09-8

End-use products (EP) 10163-GEE (GWN-1708 F, 1.6 pounds ai/gal suspension concentrate)

N N

O

H3C

CH3

CH3
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3.2 Physical/Chemical Characteristics

Fenazaquin has a log octanol/water partition coefficient (log Kow) of >3.0 and is slightly water

soluble indicating that it is fat soluble. However, fenazaquin has a molecular weight of 306.4 

g/mol; therefore, the potential to cross biological barriers is somewhat limited. Based on 

laboratory and field studies, fenazaquin was found to be persistent and immobile under most 

environmental conditions. The vapor pressure of fenazaquin is considered low (1.4x10-7 mm Hg

at 25 oC), limiting the potential for inhalation exposure. A summary of the physical/chemical 

characteristics of fenazaquin is provided in Appendix C.

3.3 Pesticide Use Pattern

Gowan has proposed to add almond and cherry uses to the GWN-1708 F label as summarized in 

Table 3.3 below. 

Table 3.3 Summary of Proposed Directions for Use of Fenazaquin (Label GWN-1708F, 10163-GEE).

Application. 

Timing, 

Type, and 

Equip.

Formulation

[EPA Reg. 

No.]

Applic. 

Rate 

(lb ai/A)

Max. No. 

Applic. 

per Season

Max. 

Seasonal 

Applic. Rate

lb ai/A

(fl oz/A)

PHI1

(days)

Use Directions and 

Limitations

Almonds

Foliar spray

GWN-1708F; 

10163-GEE;

Suspension 

concentrate

0.45 1

0.45

(36)

7

Ground application in a 

minimum of 100 gallons 

water/A

Aerial application in a 

minimum of 5 gallons 

water/A.

Do not apply more than 

one application per year. 

Cherries

Foliar spray

GWN-1708F; 

10163-GEE;

Suspension 

concentrate

0.45 1

0.45

(36)

3

Ground application in a 

minimum of 50 gallons 

water/A

Aerial application in a 

minimum of 5 gallons 

water/A.

Do not apply more than 

one application per year.

1 PHI = Preharvest interval

3.4 Anticipated Exposure Pathways

RD has requested an assessment of human health risk to support the proposed new use of 

fenazaquin on almonds and cherries. Humans may be exposed to fenazaquin in food and 

drinking water, since fenazaquin may be applied directly to growing crops and application may 

result in fenazaquin reaching surface and ground water sources of drinking water. There are 

ornamental residential uses of fenazaquin, so there are likely to be exposures in residential or 

non-occupational 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 
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post-application exposure for workers re-entering treated fields. 

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

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

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

exposure assessment. 

3.5 Consideration of Environmental Justice

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

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

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

(http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf. As a part of every pesticide risk 

assessment, OPP considers a large variety of consumer subgroups according to well-established 

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

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

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

Extensive data on food consumption patterns are compiled by the USDA under the 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, and ethnic group. 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 post-application are 

evaluated. Further considerations are currently in development as OPP has committed resources 

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

bystanders and farm workers as well as lifestyle and traditional dietary patterns among specific 

subgroups.

4.0 Hazard Characterization and Dose-Response Assessment

Fenazaquin is a quinazoline-derived insecticide used to control mites and whiteflies. 

Fenazaquin’s pesticidal mode of action is through inhibition of the mitochondrial electron 

transport at the Complex I site (NADH-ubiquinone reductase). There are no mammalian 

molecular data to confirm this mode of action in the test animals.

4.1 Toxicology Studies Available for Analysis

The toxicity studies available for risk assessment include an acute toxicity battery; subchronic 

oral studies in rats, hamsters, and dogs; subchronic dermal study in rabbits; chronic toxicity 

studies in rats and dogs; carcinogenicity studies in rats and hamsters; developmental toxicity 

studies in rats and rabbits; a 2-generation reproduction study in rats; a battery of mutagenicity 

and genotoxicity studies; an acute neurotoxicity study in rats; metabolism and pharmacokinetic 

studies in rats; and an immunotoxicity study in rats.
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Three studies, a 21-day dermal toxicity in rabbits, a developmental toxicity in rabbits, and an 

acute neurotoxicity study, were previously identified to have deficiencies. These studies were 

further evaluated in the context of the toxicity results from the entire database. The results of this 

evaluation were presented to HED Hazard and Science Policy Council (HASPOC). The Council 

conducted a thorough analysis of all the available toxicity and exposure information for 

fenazaquin, and recommended upgrading the classification and not requiring new studies with 

respect to (1) acute neurotoxicity, (2) subchronic dermal toxicity, and (3) developmental toxicity 

study in rabbits. The requirements for a subchronic inhalation toxicity study and a subchronic 

neurotoxicity study in rats were also waived (HASPOC 10 April 2014; TXR 0056942). 

4.2 Absorption, Distribution, Metabolism and Excretion (ADME)

ADME was evaluated in rats of both sexes under the following scenarios: A single or repeated 

oral low dose administration (1 mg/kg); and a single oral high dose administration (30 mg/kg). 

Fenazaquin demonstrated rapid absorption, systemic distribution, extensive metabolism, and near 

complete excretion within 72 hours. Fenazaquin distribution does not correlate with organspecific toxicity nor is it indicative of bioaccumulation potential. 

Rats absorbed 65% of the orally administered dose (AD) in male rats over 48 hours. The data 

collected in male and non-pregnant female rats at 1 mg/kg suggests a time to peak plasma level

(tmax) between 4-8 hrs. The plasma elimination half-life (t1⁄2) could not be ascertained due to the 

limitations of the pharmacokinetic study’s design. Fenazaquin residues were distributed in low

and insubstantial levels (<0.04% AD) throughout the rat carcass. The majority of the AD was 

eliminated from the rat within 48 hrs (97% AD); and feces was the primary route of elimination 

with the parent compound accounting for 1.2-4.2% AD. 

Fenazaquin was extensively metabolized in rats, and the major metabolites were AN-1 (found in 

urine), and the fecal metabolites F-1, F-2 and F-3 (as shown in Appendix B). Based on 

characterization of metabolites, metabolism was mostly the result of cleavage separating the two 

aromatic rings or oxidation of the tert-butyl group (to either a hydroxyl or carboxyl group).

4.2.1 Dermal Absorption

The registrant submitted an in vitro dermal penetration study (OECD 428), the results suggests a 

dermal absorption factor (DAF) of 0.5-7.3%. In the absence of an in vivo dermal absorption 

study, a definitive DAF could not be established for use in risk assessment with respect to the 

dermal penetration guideline (OCSPP 870.7600).

4.3 Toxicological Effects

The most consistently observed effects of fenazaquin exposure across species, genders, and 

treatment durations were decreases in body weight, food consumption, and food efficiency. The 

effects on body weight and food consumption were consistent with the commonly observed 

findings for compounds which disrupt mitochondrial respiration. Other effects noted were mild 

dehydration and certain clinical signs seen at relatively high dose levels in the acute 

neurotoxicity study. These clinical signs, which included increased foot splay, decreased motor 
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activity, sluggish arousal, unusual posture, abnormal gait, and altered response to auditory 

stimuli were seen in the absence of any neuropathological changes and were not considered to be 

related to neurotoxicity. In a 90-day study in hamsters, treated animals had an increased 

incidence of testicular hypospermatogenesis and reduced testicular and prostate weight; 

however, these findings were not replicated in the hamster carcinogenicity study which suggest 

the effects were transient or reversible.

Fenazaquin did not cause any developmental or reproductive toxicity at the doses tested in rats 

and rabbits. In the rat study, developmental toxicity was not observed in the presence of maternal 

toxicity (i.e. decreases in body weight gain, food consumption, and food efficiency). In the rabbit 

study, no developmental or maternal toxicity was seen. In the reproduction study, systemic 

toxicity manifested in parental animals as excessive salivation and decreased body weight and 

food intake; in offspring as decreased body weight gain; and there was no observed reproductive 

toxicity. Therefore, there is no developmental toxicity or reproductive susceptibility with respect 

to fetal and developing young animals with in utero and postnatal exposures.

Carcinogenicity was evaluated in the hamster instead of the mouse because the hamster was 

found to be more sensitive to the effects of fenazaquin than mice due to slower elimination 

kinetics for hamster. In a three-month feeding study in the mouse, it was found that 6-22x higher 

dose levels were required to elicit a comparable effect in mice than in the hamster. The results of 

the rat and hamster carcinogenicity studies demonstrated no increase in treatment-related tumor 

incidence. Therefore, fenazaquin was classified as “Not likely to be Carcinogenic to Humans.”

Fenazaquin did not cause mutagenicity, genotoxicity, neurotoxicity, or immunotoxicity. 

Fenazaquin did not demonstrate any systemic toxicity in a 21-day dermal toxicity study in 

rabbits up to the limit dose (1000 mg/kg/day). 

Fenazaquin has high acute oral toxicity (Category II); and low acute toxicity by dermal and 

inhalation routes of exposure (Categories IV and III, respectively). Fenazaquin is not a skin 

irritant (Category III), but it is minimally irritating to the eye (Category IV). Fenazaquin is 

considered to be a dermal sensitizer; Technical Review Branch (TRB) / Registration Division 

(RD) made this recommendation due to the lack of an acceptable dermal sensitization study

demonstrating otherwise.

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

The 10x FQPA Safety Factor can be reduced to 1x because the toxicity database is complete, 

there is no evidence of sensitivity/susceptibility in the developing organism, no evidence of 

neurotoxicity, and no residual uncertainty in the exposure data. The details are discussed below.

4.4.1 Completeness of the Toxicology Database

As described in Section 4.1, HED HASPOC recommended upgrading and not requiring new 

studies for acute neurotoxicity study, subchronic dermal toxicity study, and developmental study 

in rabbits. In addition, the HASPOC recommended waiving the requirements for a subchronic 

inhalation study and a subchronic neurotoxicity study. In the presence of these recommendations, 
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the toxicity database for fenazaquin was considered complete and sufficient for assessing 

susceptibility to infants and children as required by FQPA.

4.4.2 Evidence of Neurotoxicity

There are no indications in any of the studies available that the nervous system is a target for 

fenazaquin. In the acute neurotoxicity study in rats at the highest dose tested (130 mg/kg/day in 

males and 120 mg/kg/day in females), the clinical signs such as mild dehydration, increased foot 

splay, decreased motor activity, sluggish arousal, unusual posture, abnormal gait, and altered 

response to auditory stimuli were observed on Day 1 only. An increase in the incidence of 

minimal nerve fiber degeneration was also reported in the high dose males, but in females, this 

incidence was greater in controls than that in the high dose group. Considering the findings in 

both genders, the finding of minimal nerve fiber degeneration was considered to be equivocal 

because when the data for both sexes are combined the incidence for the high dose animals was 

no different from the controls. The neuropathology findings seen in this study were also 

evaluated by EPA’s Office of Research and Development (ORD); the conclusion was that 

minimal nerve fiber degeneration found in the highest dose animal in this study should not be 

considered as a treatment-related effect for the reasons just discussed. Therefore, in the absence 

of neuropathology, the observed clinical signs were not considered to be related to neurotoxicity. 

Additional supporting evidence for this conclusion was that in the repeated dosing studies in rats, 

dogs, and hamsters, there were no clinical signs indicative of neurotoxicity; no gross/microscopic 

pathology findings were observed in central or peripheral nervous systems in these studies. 

The HASPOC evaluated the available toxicity data in association with the possible need for a 

subchronic neurotoxicity study, and it was determined that a subchronic neurotoxicity study was 

not needed at this time because 1) indications of treatment-related clinical signs in the ACN were

well-characterized; 2) effects seen in ACN were observed at doses higher than current PODs; 

and 3) there was no indication of treatment-related neurotoxicity observed in any repeated dosing 

studies. In the absence of gross neurotoxicity or neuropathology findings in the available 

database, a developmental neurotoxicity study is not required.

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

Susceptibility/sensitivity in the developing animals was evaluated in developmental toxicity 

studies in rats and rabbits as well as a reproduction and fertility study in rats.

In the rabbit developmental toxicity study, toxicity was not observed in dams or fetuses up to 13 

mg/kg/day; HED excluded the high dose group (60 mg/kg/day) because of a loss of nearly a third 

of that dose group due to technical difficulties that were not deemed to be test substance related. 

Despite the technical difficulties, the surviving animals at the 60 mg/kg/day dose group did not

demonstrate any maternal or fetal toxicity. Additionally, there were no fetal effects up to the 

highest dose tested (100 mg/kg/day) in a range-finding developmental toxicity study in rabbits. 

In the rat developmental toxicity study at the highest dose tested (40 mg/kg/day), maternal 

toxicity consisting of decreases in food consumption and body weight gain occurred in the 

absence of any developmental toxicity in fetuses. 
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In the reproduction study, the offspring effects (i.e., decreased body weight gain during lactation) 

occurred only in the presence of parental toxicity (i.e., excessive salivation and decreased body 

weight, body weight gain, and food intake). Therefore, there is no evidence of 

sensitivity/susceptibility in the developing or young animal. Clear NOAELs and LOAELs are 

available for all the parental and offspring effects. Therefore, there are no residual pre- or postnatal concerns. 

4.4.4 Residual Uncertainty in the Exposure Database

There are no residual uncertainties in the exposure database. Since the dietary and non-dietary 

exposure estimates were based on several conservative assumptions, HED does not believe that 

the exposure estimates are underestimated. The acute and chronic dietary assessments conducted 

with DEEM-FCID were screening level analyses. The assessments utilized tolerance values, 

default processing factors, and assumed that 100% of the registered and proposed crops were

treated with fenazaquin. The dietary exposure analyses also assumed that all drinking water will 

contain fenazaquin at the highest EDWC levels modeled by Environmental Fate and Effects 

Division (EFED). Therefore, the dietary exposure analyses do not underestimate risk from acute 

or chronic dietary exposure to fenazaquin. Similarly, HED does not believe that the non-dietary 

residential exposures are not underestimated because they are also based on conservative 

assumptions, including maximum application rates, and standard values for unit exposures, 

amount handled as described in the Residential SOPs.

4.5 Toxicity Endpoint and Point of Departure Selection

4.5.1 Dose-Response Assessment

The doses and endpoints selected for dietary risk assessments are shown in Table 4.5.4.1. For 

acute dietary exposure, the results from the immunotoxicity study were considered in selecting 

toxicity endpoints and points of departure (POD) for risk assessment. The NOAEL of 15 

mg/kg/day was selected as the POD based on clinical signs (i.e. general ataxia/hypoactivity) 

observed after a single exposure at the LOAEL of 30 mg/kg/day. The endpoint is appropriate for 

this exposure scenario since the effects were seen after a single oral administration. In addition, it 

is also protective of the clinical signs (i.e., mild dehydration) seen in the acute neurotoxicity 

study at 60 mg/kg (LOAEL). An acute reference dose (aRfD) of 0.15 mg/kg/day was derived 

from the NOAEL with the application of an Uncertainty Factor (UF) of 100x (10x inter-species 

extrapolation, 10x intra-species variations factor).

A separate endpoint of concern for pregnant females (13-49 years of age) was not selected since 

no endpoints attributable to a single dose were identified in the developmental toxicity studies in 

rats and rabbits.

For chronic dietary exposure, the toxicity endpoints of decreases in body weight, food 

consumption, and food efficiency were selected, and these effects were seen at similar dose 

levels in both subchronic (15 mg/kg/day) and chronic (12 mg/kg/day) oral toxicity studies in 

dogs. The NOAELs were the same for both chronic and subchronic toxicity studies in dogs. The 

results from these two studies demonstrated no increase in severity with increased treatment 
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durations. Hence, the subchronic and chronic toxicity studies in dogs were appropriate to be 

employed as co-critical studies for toxicity end point and point of departure selections for the 

chronic exposure scenario. A chronic reference dose (cRfD) of 0.05 mg/kg/day was derived from 

a NOAEL of 5 mg/kg/day and an UF of 100x. While the NOAEL of the chronic toxicity study in 

the hamster (2 mg/kg/day) is lower than that of dogs, it was not selected because it was 

considered to be an artifact of dose-selection.

For the short term incidental oral exposure risk assessment, the toxicity endpoints and NOAEL 

seen in the subchronic and chronic dog studies were deemed appropriate for the short term 

incidental oral exposure scenario since the effects in the dog studies were similar in both 

subchronic and chronic toxicity studies. Similar effects were also seen in the reproduction study.

Dermal endpoints for both short- and intermediate-term exposures were not selected because an 

in vitro dermal penetration study suggested that the dermal absorption was less than 8%, and 

there were no systemic effects observed in the 21-day dermal toxicity study in rabbits up to the 

limit dose (1000 mg/kg/day). There was no treatment related toxic effects observed in the oral 

studies with respect to developmental and reproductive toxicity or susceptibility; additionally, no 

toxic effects were observed with respect to neurotoxicity or immunotoxicity. 

An inhalation study is not included in the available database (and the requirement has been 

waived as discussed in Section 4.1) so inhalation endpoints for occupational and residential 

exposures were derived from oral studies. For short- and intermediate-term inhalation, the 

NOAEL of 5 mg/kg/day was used as the POD from co-critical subchronic and chronic toxicity 

studies in dogs, with LOAELs of 15 and 12 mg/kg/day, respectively, based on decreased body 

weight and food consumption/efficiency.

There are no long-term dermal or inhalation scenarios anticipated for this risk assessment

4.5.2 Recommendation for Combining Routes of Exposure for Risk Assessment

HED has considered the potential for concurrent exposure via oral, dermal, and inhalation routes; 

HED aggregates exposure from different routes for each population if the same toxic effects are 

seen for that duration of exposure by each route. Since oral and inhalation endpoints are based on 

the same effects (i.e., decreases in body weight, food consumption, and food efficiency), these 

routes of exposure may be combined for residential exposure risk assessment. 

4.5.3 Cancer Classification and Risk Assessment Recommendation

Fenazaquin is classified as “Not likely to be Carcinogenic to Humans” based on the absence of a 

treatment-related increase in tumor incidence in adequately conducted carcinogenicity studies in 

hamsters and rats.
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4.5.4 Summary of Points of Departure and Toxicity Endpoints Used in Human Risk 

Assessment

Table 4.5.4.1 presents a summary of the endpoints selected for fenazaquin for use in risk 

assessments. A summary of the acute toxicity categories for the technical material are included 

in Appendix A.

Table 4.5.4.1. Summary of Toxicological Doses and Endpoints for use in Dietary and Non-Occupational Human Health 

Risk Assessments

Exposure Scenario Point of 

Departure 

(POD)

Uncertainty / FQPA 

Safety Factors

RfD, PAD, and

LOC for Risk 

Assessment

Study and Toxicological Effects

Acute Dietary

General population 

(including infants and 

children)

And

Females (13-49 years)

NOAEL= 

15 mg/kg/day

UFA= 10x

UFH= 10x

FQPA SF= 1x

aRfD = 0.15

mg/kg/day

aPAD = 0.15

mg/kg/day

Immunotoxicity – Rat

LOAEL = 30 mg/kg/day

Based on clinical signs (general 

ataxia/hypoactivity) observed in 1 

animal on Day 02 and 3 animals on 

Day 03 of dosing. 

Chronic Dietary

All populations

NOAEL= 

5 mg/kg/day

UFA= 10x

UFH= 10x

FQPA SF= 1x

cRfD = 0.05 

mg/kg/day

cPAD = 0.05 

mg/kg/day

Co-Critical: Subchronic and Chronic 

Toxicity – Dog

Subchronic Toxicity – Dog

LOAEL = 15 mg/kg/day

Based on decreased body weight and 

food consumption/efficiency.

Chronic Toxicity – Dog

LOAEL = 12 mg/kg/day 

Based on decreased body weight and 

food consumption/efficiency

Incidental Oral

Short Term

(1-30 days)

NOAEL =

5 mg/kg/day

UFA= 10x

UFH= 10x

FQPA SF= 1x

LOC = 

MOE = 100

Co-Critical: Subchronic and Chronic 

Toxicity – Dog

Same as Chronic Dietary

Inhalation 

Short Term (1-30 days)

And

Intermediate Term 

(1-6 months)

NOAEL =

5 mg/kg/day

UFA= 10x

UFH= 10x

FQPA SF= 

LOC = 

MOE = 100

Co-Critical: Subchronic and Chronic 

Toxicity – Dog

Same as Chronic Dietary

Dermal 

Short Term (1-30 days)

And

Intermediate Term 

(1-6 months)

There is no identified hazard for this scenario because there was no observed systemic toxicity in rats 

treated up to the limit dose (1000 mg/kg/day). Additionally, developmental toxicity, reproductive 

susceptibility, neurotoxicity, and immunotoxicity effects were not observed in the database.

Cancer (oral, dermal, 

and inhalation)

Classification: “Not likely to be Carcinogenic to Humans” based on the absence of significant tumor 

increases in two adequate rodent carcinogenicity studies.

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

mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL 

= no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UFA = extrapolation 

from animal to human (interspecies). UFH = potential variation in sensitivity among members of the human population 

(intraspecies). FQPA SF = FQPA Safety Factor. PAD = population adjusted dose (a = acute, c = chronic). RfD = reference dose. 

MOE = margin of exposure. LOC = level of concern. N/A = not applicable.
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Table 4.5.4.2: Summary of Toxicological Doses and Endpoints for use in Occupational Human Health Risk Assessments

Exposure Scenario Point of 

Departure 

(POD)

Uncertainty / FQPA 

Safety Factors

RfD, PAD, and 

LOC for Risk 

Assessment

Study and Toxicological Effects

Inhalation 

Short Term (1-30 days)

And

Intermediate Term 

(1-6 months)

NOAEL =

5 mg/kg/day

UFA= 10x

UFH= 10x

LOC = 

MOE = 100

Co-Critical: Subchronic and Chronic 

Toxicity – Dog

Same as Chronic Dietary exposure 

scenario in Table 4.5.4.1

Dermal

Short Term (1-30 days)

And

Intermediate Term 

(1-6 months)

There is no identified hazard for this scenario because there was no observed systemic toxicity in rats 

treated up to the limit dose (1000 mg/kg/day). Additionally, developmental toxicity, reproductive 

susceptibility, neurotoxicity, and immunotoxicity effects were not observed in the database.

Cancer (oral, dermal, 

and inhalation)

Classification: “Not likely to be Carcinogenic to Humans” based on the absence of significant tumor 

increases in two adequate rodent carcinogenicity studies.

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 Metabolite/Degradate Residue Profile

5.1.1 Summary of Plant and Animal Metabolism Studies

Metabolism studies in apples and citrus were previously evaluated to support tolerances in/on 

imported apple, citrus fruits (except grapefruit), and pear. New metabolism studies conducted 

with grapes and corn; lettuce, wheat and radish (confined rotational); poultry and goat. An

aerobic soil metabolism study and aerobic aquatic metabolism study were submitted to support 

the proposed new uses. It should be noted that subsequent to the completion of the residue 

chemistry memo (D391810, S. Funk, 07/25/12) and ROCKS meeting decision (D397773, I. 

Negrón-Encarnación, 04/18/12) Gowan amended the proposed label to include only almonds and 

cherries. There is one livestock (cattle) feed item, almond hulls, however, based on a maximum 

reasonably based diet (MRBD), no residues are anticipated in the livestock commodities. 

The residue chemistry database is adequate for determining residues of concern. Metabolism 

studies were conducted with fenazaquin radiolabled in the phenyl ring or in the quinazoline ring. 

Parent fenazaquin is a major residue in corn grain, corn stover, grape, orange, and apple. 

Fenazaquin dimer, a photolysis product, is absent in grapes, but is a major metabolite in corn 

stover and apple, and a minor metabolite in corn grain. Other metabolites are generally <10% of 

the Total Radioactive Residue (TRR) across all matrices and PHIs. The exceptions are 

metabolite I (2-hydroxy fenazaquin) and metabolite C (fenazaquin alcohol) which were observed 

in grapes at maximum concentrations of 26% and 12.9 % of the TRR, respectively. However, 

about half of metabolite I is conjugated. See Appendix D for a list and description of all 

metabolites.
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A confined rotational crop study (1X) was conducted with lettuce, wheat, and radish. 

Fenazaquin was found at concentrations > 0.01 ppm only in 30-day PBI radish root (0.03 ppm). 

Fenazaquin was extensively degraded/metabolized in the confined rotational crop study to 

multiple metabolites/degradates that were also observed in the primary crop metabolism studies. 

With a 120-day plant back interval (PBI) for root and tuber and bulb vegetables (and 30 days for 

all other crops), there will be no significant rotational crop residues. 

The livestock metabolism studies were performed by administrating radiolabeled fenazaquin to 

poultry and goats. The highest total radioactive residues (TRR) were in the fat and liver of goats 

and the fat of poultry, suggesting that fenazaquin partitions into fat and is detoxified via the liver

in ruminants. In addition, fenazaquin was a major residue in milk. Fenazaquin was absent in 

goat muscle, kidney, and liver and was present at low levels (<10% TRR or <0.01 ppm) in 

poultry muscle and eggs and absent in liver. Major metabolites in goat were metabolite M29 in 

muscle, kidney, and liver; metabolite M34 in liver; and metabolite J in milk. Metabolite J in 

milk was at a low absolute amount, <0.01 ppm. The major metabolite in muscle, liver, and eggs 

of poultry was metabolite I. 

5.1.2 Summary of Environmental Degradation

Fenazaquin is persistent and immobile in terrestrial and aquatic environments. Degradation 

products of fenazaquin can be classified according to their formation by cleavage of the ether 

(ethoxy) linkage. This cleavage generates products with only the tert-butylphenyl group or the 

quinazoline group. The quinazoline products form mostly 4-quinazolinol and 2,4-quinazolinediol. Linkage intact products are reactions involving the quinazoline part of the molecule. Major

degradation products (> 10% of applied radioactivity) of fenazaquin are 4-(2-(4-(1,1-

imethylethyl)phenyl)ethoxy)quinazolone (Metabolite 1), and 2-Methyl-2-(4-{2-[(2-oxo-1,2-

dihydroquinazolin-4-yl)oxy]ethyl}phenyl) propanoic acid (Metabolite 29).

The environmental fate studies showed that fenazaquin has a half-life from 51 to 123.8 days in 

aerobic soil and 58.7 to 133.3 days in aerobic aquatic environments. Two major degradates were 

identified in the aerobic aquatic metabolism, metabolite 1 and metabolite 29. The half-life of 

fenazaquin total toxic residues (parent + metabolite 1 + metabolite 29) ranged from 73 to 197 

days in aerobic soil metabolism studies, and 65 to 291 days in aerobic aquatic environments. 

Additionally, the mobility of the metabolites, especially Metabolite 29, is expected to be higher 

than parent fenazaquin. 

5.1.3 Comparison of Metabolic Pathways

Fenazaquin is extensively metabolized in rats, resulting with the major metabolites of AN-1 

(found in urine) and the fecal metabolites (F-1, F-2 and F-3) (see Appendix B). Based on 

characterization of metabolites, metabolism was mostly the result of cleavage separating the two 

aromatic rings or oxidation of the tert-butyl group (to either a hydroxyl or carboxyl group).

The predominant residues in plants are parent fenazaquin and its dimer, which is a photolysis 

product. The dimer is unlikely to be cleaved back to the parent. Fenazaquin tends to be a 
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surface residue and metabolizes via oxidation of the t-butyl methyl group, oxidation of the C-2 of 

the quinazoline ring, and hydroxylation/cleavage of the ether linkage.

The aquatic metabolism studies showed metabolite 1 and metabolite 29 as major metabolites. 

Metabolites are formed via cleavage of the ether linkage.

5.1.4 Residues of Concern Summary and Rationale

The residue of concern for risk assessment and tolerance enforcement in primary and rotational 

crops is parent fenazaquin. Parent fenazaquin, metabolite 1 and metabolite M29 are included as 

residues of concern in drinking water. Table 5.1.4 summarized the residues of concern for 

fenazaquin.

Plants: The predominant residues in plants are parent fenazaquin and its dimer. The dimer is 

excluded as a residue of concern since it is unlikely to be cleaved back to the parent, and is not 

likely to be bioavailable after ingestion due to its high molecular weight and lipophilic 

properties. Metabolite I was not considered a residue of concern, since about half of it is 

conjugated and it was observed in grapes 76 days after treatment (DAT), which is much longer 

than the proposed PHI of 7 days. Although metabolite C was 12.9% of the TRR in grapes 49 

DAT, the absolute amount (0.046 ppm) is fairly low. Metabolite C was absent or <10% TRR in 

other crops studied. Therefore, it is not considered a residue of concern. The residue of concern 

for risk assessment and tolerance enforcement in primary crops is parent fenazaquin.

Rotational Crops: The confined rotational crop studies showed similar results to those of 

primary crops. The residue of concern for risk assessment and tolerance enforcement in 

rotational crops is parent fenazaquin.

Livestock: Metabolism studies in goat showed parent fenazaquin and metabolite J as the major 

metabolites observed in milk. The latter was identified as 4-hydroxyquinazoline (metabolite J),

which doesn’t appear to be more toxic than parent fenazaquin. In addition, the absolute amount 

of metabolite J is below 0.01 ppm. Fenazaquin was the major component of the residue in fat, 

with no single metabolite identified above 1.1% TRR. Based on this, the residue of concern for 

risk assessment and tolerance enforcement in fat and milk of ruminants is parent fenazaquin. 

Two different major metabolites were observed in meat, liver and/or kidney, metabolite M29 and 

metabolite M34. The latter is excluded as a residue of concern since it was only observed as a 

major metabolite in goat liver (15.3% TRR) and it appears to be very water soluble. The residue 

of concern for risk assessment and tolerance enforcement in kidney, liver and muscle of 

ruminant is parent fenazaquin and metabolite M29. Based on the proposed uses of fenazaquin, 

there is no reasonable expectation of residues in poultry; however, the residues of concern were 

identified in case new uses are proposed. Parent fenazaquin and metabolite I were the major 

residues observed in poultry. Both are recommended as residues of concern in poultry 

commodities for tolerance enforcement and risk assessment. 

Water: The aquatic metabolism studies showed metabolite 1 and metabolite 29 as major 

metabolites. These are structurally similar to parent fenazaquin; therefore, they are not likely to 

be less toxic than the parent. The ROCKS recommends that parent fenazaquin, metabolite 1 and 
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metabolite M29 are included as residues of concern in drinking water. For the risk assessment, it 

is assumed that the M29 and metabolite 1 have a similar toxicity to the parent. Drinking water 

exposure is estimated for total residues of fenazaquin, M29 and metabolite 1. 

Table 5.1.4. Summary of Metabolites and Environmental Transformation Products to be Included in the 

Risk Assessment and Tolerance Expression1

Matrix Residues included in Risk Assessment Residues included in Tolerance 

Expression

Plants Primary Crop Fenazaquin Fenazaquin

Rotational Crop Fenazaquin Fenazaquin

Livestock Ruminant Milk, Fat: Fenazaquin 

Liver, Kidney, Meat: 

Fenazaquin and Metabolite M29

Milk, Fat: Fenazaquin 

Liver, Kidney, Meat: 

Fenazaquin and Metabolite M29

Poultry Fenazaquin and 

Metabolite I

Fenazaquin and 

Metabolite I

Drinking Water Fenazaquin, Metabolite 29 and 

Metabolite 1 

Not Applicable

1 Fenazaquin is 4-[[4-(1,1-dimethylethyl)phenyl]ethoxy]quinazoline; Metabolite M29 is 2-(4-{2-[(2-

hydroxyquinazolin-4-yl)oxy]ethyl}phenyl)-2-methylpropanoic acid and its tautomer 2-Methyl-2-(4-{2-[(2-oxo-1,2-

dihydroquinazolin-4-yl)oxy]ethyl}phenyl)propanoic acid; Metabolite I is quinazoline-2,4-diol and its tautomer

quinazoline-2,4(1H,3H)-dione; Metabolite 1 is 4-[2-(4-tert-butyl-phenyl)-ethoxy]-quinazolin-2-ol and its tautomer

4-[2-(4-tert-butylphenyl)ethoxy]quinazolin-2(1H)-one.

5.2 Food Residue Profile

The submitted magnitude of the residue data, summarized in Table 5.2.1, are adequate for risk 

assessment and tolerance assessment (D391810, S. Funk, 07/25/12). Residues of fenazaquin 

were detected at low levels, indicating that there will be low exposure to fenazaquin in food. 

Processing studies were not conducted for processed commodities associated with proposed 

crops.

Table 5.2.1. Summary of Residues from Field Trials with Fenazaquin

Crop 

Matrix Analyte

Applic. 

Rate

(lb 

ai/acre)

PHI 

(days) n

1

Residues (ppm)

Min.2 Max.2 LAFT3 HAFT3 Median3 Mean3 SD3

STONE FRUIT, Proposed Cherry Use = 0.45 lb ai/acre total application rate, 3-day PHI

Cherry, 

sweet/tart

Fenazaq

uin 0.45 3 12 0.233 0.965 0.255 0.914 0.521 0.587 0.246

Cherry, 

sweet/tart Dimer 0.45 3 12 <0.01 0.0165 0.01 0.0163 0.01 0.0105 0.0018

TREE NUTS, Proposed Almond Use = 0.45 lb ai/acre total application rate, 7-day PHI

Almond 

Nutmeat

Fenazaq

uin

0.44 –

0.45 7 10 <0.01 0.0116 0.01 0.011 0.010 0.010 0.0004

Almond 

Nutmeat Dimer 0.44 –0.45 7 10 <0.01 0.0360 0.01 0.0356 0.01 0.015 0.0114

Almond

Hull

Fenazaq

uin

0.44 –

0.45 7 10 0.2174 1.674 0.27 1.47 1.2 0.94 0.567

Almond 

Hull Dimer 0.44 –0.45 7 10 <0.01 0.1647 0.015 0.154 0.034 0.0578 0.0574

1 Number of samples, typically 2X number of trials.
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2 Values based replicates and not averages.

3 Values based on per-trial averages. LAFT = Lowest Average Field Trial, HAFT = Highest Average Field Trial, SD = Standard 

Deviation. For computation of the LAFT, HAFT, median, mean, and standard deviation, values < LOQ (0.01 ppm) are assumed 

to be at the LOQ.

5.3 Water Residue Profile

Estimated surface water and groundwater concentrations were provided by EFED (D394030, J. 

Hetrick, 03/08/12) and are shown in Table 5.3. The dietary exposure assessment used the peak 

concentration values of 5.74 ppb for acute and 2.09 ppb for chronic assessments. The drinking 

water assessment is based PRZM and EXAMS modeling for all currently registered and 

proposed fenazaquin uses. All Tier II surface water modeling was corrected for default percent 

cropped area (PCA) of 0.87.

The drinking water assessment was conducted using the total toxic residue (TTR) approach. The 

residues considered in this assessment include fenazaquin (parent), Metabolite 1, and Metabolite 

29.

Table 5.3. Summary of Estimated Surface Water and Groundwater Concentrations for Fenazaquin

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

Acute 5.74

Chronic (non-cancer) 2.09 0.704

Chronic (cancer) 1.33

a From the Tier II PRZM-EXAMS - Index Reservoir model. Input parameters are based on MI cherry scenario

b From the SCI-GROW model.

It should be noted that based on personal communication with EFED, the PRZM-GW modeling would not produce 

EWDCs higher that those presented here (email from D. Spatz to C. Olinger 5/19/14)

5.4 Dietary Risk Assessment

5.4.1 Description of Residue Data Used in Dietary Assessment

The acute and chronic dietary analysis for non-cancer risk assessment assumed tolerance level

residues for all registered and proposed crops. Default processing factors were used for all 

processed commodities.

5.4.2 Percent Crop Treated Used in Dietary Assessment

The acute and chronic dietary analyses assumed that 100% of the crop was treated (100% CT). 

5.4.3 Acute Dietary Risk Assessment

An unrefined acute dietary assessment was conducted. The assumptions of this dietary 

assessment included tolerance levels residues for all proposed and registered crops, default 

processing factors, and 100% CT was assumed. A tier II (PRZM-EXAMS) EDWC derived 

through EFED modeling which is unlikely to underestimate the concentration of fenazaquin in 
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drinking water was utilized. The surface water EDWC (5.74 μg/L) was incorporated directly 

into the dietary assessment (D394030, J. Hetrick, 03/08/12).

As shown in Table 5.4.6, the acute dietary (food and drinking water) exposure to fenazaquin is 

below HED’s level of concern [i.e., <100% of the acute Population Adjusted Dose (aPAD)] for 

the general U.S. population and all population subgroups. The acute dietary exposure estimates 

at the 95th percentile are 3% of the aPAD for the general U.S. population and 10% of the aPAD 

for children 1-2 years of age, the most highly exposed population subgroup.

5.4.4 Chronic Dietary Risk Assessment

An unrefined chronic dietary assessment was conducted. Tolerance level residues, 100% CT, 

and default processing factors were used to determine the chronic dietary exposure and risk 

estimates. A tier II EDWC derived through EFED modeling which is unlikely to underestimate 

the concentration of fenazaquin in drinking water was utilized. The ground water EDWC (2.09 

μg/L) was incorporated directly into the dietary assessment (D394030, J. Hetrick, 03/08/12).

As shown in Table 5.4.6, the chronic dietary (food and drinking water) exposure to fenazaquin is 

below HED’s level of concern (<100% cPAD) for the general U.S. population and all population 

subgroups. The chronic dietary exposure estimates are 2% of the cPAD for the general U.S. 

population and 10% of the cPAD for children 1-2 years of age, the most highly exposed 

population subgroup.

5.4.5 Cancer Dietary Risk Assessment

A cancer dietary risk assessment was not conducted because there was no evidence of 

carcinogenicity to humans based on lack of carcinogenic effects in the rat and mouse 

carcinogenicity studies.

5.4.6 Summary Table

Table 5.4.6. Summary of Dietary (Food and Drinking Water) Exposure Analysis for Fenazaquin Using 

DEEM-FCID

Population Subgroup

Acute Dietary 

(95th Percentile) Chronic Dietary

Dietary Exposure 

(mg/kg/day) % aPAD Dietary Exposure (mg/kg/day) % cPAD

General U.S. Population 0.004348 3 0.000949 2

All Infants (< 1 year old) 0.007455 5 0.001831 4

Children 1-2 years old 0.015404 10 0.004753 10

Children 3-5 years old 0.011604 8 0.003358 7

Children 6-12 years old 0.006134 4 0.001481 3

Youth 13-19 years old 0.003965 3 0.000777 2

Adults 20-49 years old 0.002985 2 0.000586 1

Adults 50-99 years old 0.002568 2 0.000619 1

Females 13-49 years old 0.003034 2 0.000613 1

*The subpopulation with the highest risk estimates
Fenazaquin Human Health Risk Assessment DP No. D391819

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6.0 Residential (Non-Occupational) Exposure/Risk Characterization

There are no residential uses being requested at this time. However, there are existing residential 

uses that were reassessed using the updates to the 2012 HED Residential SOPs. 

6.1 Residential Handler Exposure

There are existing residential ornamental uses that were reassessed using the updates to the 2012 

HED Residential SOPs. It is assumed that most residential uses will result in short-term (1-30 

day) exposures. Residential handlers are assumed to be wearing short-sleeved shirts, short pants, 

shoes, and socks while handling fenazaquin. Because there was no dermal endpoint chosen for 

fenazaquin, risk from exposure to fenazaquin was assessed for the inhalation route only. 

Table 6.1 lists the residential handler inhalation risk estimates for ornamental treatments. 

Residential handler inhalation MOEs were not of concern to HED, and ranged from 190,000 to 

19,000,000. 

Table 6.1: Residential Handler Non-cancer Exposure and Risk Estimates for Fenazaquin.

Exposure Scenario Level of 

Concern

Inhalation Unit 

Exposure (mg/lb ai)

Maximum 

Application 

Rate1

Amount 

Handled 

Daily2

Inhalation

Dose 

(mg/kg/day)3 MOE4

Mixer/Loader/Applicator to Ornamentals

Manually Pressurized 

Handwand

100

0.018

0.003 lb 

ai/gal

5 gal 0.0000034 1,500,000

Hose-End Sprayer 0.0014 11 gal 0.00000058 8.700,000

Backpack Sprayer 0.14 5 gal 0.000026 190,000

Sprinkler Can 0.0014 5 gal 0.00000026 19,000,000

1 Based on registered label (EPA Reg. No. 10163-297).

2 Based on HED’s 2012 Residential SOPs (http://www.epa.gov/pesticides/science/residential-exposure-sop.html).

3 Inhalation Dose = Inhalation Unit Exposure (mg/lb ai) × Application Rate (lb ai/acre or gal) × Amount Handled (gallons/day) 

÷ BW (80 kg).

4 Inhalation MOE = Inhalation NOAEL (5 mg/kg/day) ÷ Inhalation Dose (mg/kg/day).

6.2 Post-Application Exposure

There is the potential for post-application exposure for individuals exposed as a result of being in 

an environment that has been previously treated with fenazaquin. However, since there is no 

adverse systemic hazard via the dermal route of exposure, and there is no incidental oral 

exposure expected from fenazaquin use on ornamental plants, a residential post-application 

assessment has not been conducted.

6.3 Residential Risk Estimates for Use in Aggregate Assessment

The recommended residential exposure for use in the adult aggregate assessment reflects 

inhalation exposure from applications to ornamentals via backpack sprayer (0.000026 

mg/kg/day). Since there is no residential incidental oral exposure expected for children 1<2 

years old on ornamental plants, the aggregate assessment for children will only include exposure 

from food and water. 
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6.4 Residential Bystander Post-application Inhalation Exposure

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 has evaluated the SAP report and has developed a Volatilization Screening Tool and a 

subsequent Volatilization Screening Analysis 

(http://www.regulations.gov/#!docketDetail;D=EPA-HQ-OPP-2014-0219). 

During Registration Review, the agency will utilize this analysis to determine if data (i.e., flux 

studies, route-specific inhalation toxicological studies) or further analysis is required for 

fenazaquin.

6.5 Spray Drift

Spray drift is a potential source of exposure to those nearby pesticide applications. This is 

particularly the case with aerial application, but, to a lesser extent, spray drift can also be a 

potential source of exposure from the ground application methods (e.g., groundboom and 

airblast) employed for fenazaquin. The agency has been working with the Spray Drift Task 

Force (a task force composed of various registrants which was developed as a result of a Data 

Call-In issued by EPA), 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). 1 The agency has also developed a policy on how to 

appropriately consider spray drift as a potential source of exposure in risk assessments for 

pesticides. The potential for spray drift will be quantitatively evaluated for each pesticide during 

the Registration Review process which ensures that all uses for that pesticide will be considered 

concurrently. The approach is outlined in the revised (2012) Standard Operating Procedures 

For Residential Risk Assessment (SOPs) - Residential Exposure Assessment Standard Operating 

Procedures Addenda 1: Consideration of Spray Drift. This document outlines the quantification 

of indirect non-occupational exposure to drift. 

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 Aggregate Risk

The acute aggregate risk is equal to the acute dietary (food and drinking water) exposure. Refer 

to Section 5.4.3.

 

1 Available: http://www.epa.gov/opp00001/factsheets/spraydrift.htm 
Fenazaquin Human Health Risk Assessment DP No. D391819

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7.2 Short-Term Aggregate Risk

There is potential short-term exposure to fenazaquin via the dietary pathway (which is 

considered background exposure) and the residential pathway (which is considered the primary

pathway). Since intermediate-term residential exposures are not likely to occur, intermediateterm aggregate risks were not assessed. The short-term aggregate exposure assessment for adults 

includes dietary (food and drinking water) and inhalation handler exposures. The most 

conservative scenario was chosen. Since there is no residential incidental oral exposure expected 

for children 1<2 years old on ornamental plants, the aggregate assessment for children will only 

include exposure from food and water. For a description of the residential exposure scenarios 

considered in the aggregate assessment, see Section 6.1. 

Table 7.2 Short-Term Aggregate Risk Calculations

Population

Short-Term Scenario

NOAEL 

mg/kg/day LOC1

Max 

Allowable 

Exposure2

mg/kg/day

Average 

Food and 

Water 

Exposure 

mg/kg/day

Residential 

Exposure 

mg/kg/day3

Total 

Exposure 

mg/kg/day4

Aggregate 

MOE (food, 

water, and 

residential)5

Adult Male 5 100 0.05 0.000949 0.000026 0.000975 5,200

1 LOC = standard inter- and intra- species uncertainty factors totaling 100

2 Maximum Allowable Exposure (mg/kg/day) = NOAEL/LOC

3 Residential Exposure = Inhalation Handler Exposure. Table 6.1.

4 Total Exposure = Avg Food & Water Exposure + Residential Exposure

5 Aggregate MOE = [NOAEL ÷/ (Avg Food & Water Exposure + Residential Exposure)]

7.3 Chronic Aggregate Risk

The chronic aggregate risk is equal to the chronic dietary (food and drinking water) exposure. 

Refer to Section 5.4.4.

7.4 Cancer Aggregate Risk

A cancer aggregate risk assessment was not conducted because there was no evidence of 

carcinogenicity to humans based on lack of carcinogenic effects in the rat and mouse 

carcinogenicity studies.

8.0 Cumulative Exposure/Risk Characterization

Unlike other pesticides for which EPA has followed a cumulative risk approach based on a 

common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as 

to fenazaquin and any other substances and fenazaquin does not appear to produce a toxic 

metabolite produced by other substances. For the purposes of this tolerance action, therefore, 

EPA has not assumed that fenazaquin has a common mechanism of toxicity with other 

substances. For information regarding EPA’s efforts to determine which chemicals have a 

common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the 

policy statements released by EPA’s Office of Pesticide Programs concerning common 
Fenazaquin Human Health Risk Assessment DP No. D391819

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mechanism determinations and procedures for cumulating effects from substances found to have 

a common mechanism on EPA’s website at http://www.epa.gov/pesticides/cumulative/.

9.0 Occupational Exposure/Risk Characterization

9.1 Short-Term Handler Risk

Occupational exposures are expected to occur from the proposed fenazaquin use on almonds and 

cherries. Only short-term (1-30 consecutive days) dermal and inhalation exposures are expected 

because fenazaquin has been proposed for use only once per season. Additionally, for inhalation 

exposures, the POD selected are considered protective of both short- and intermediate-term 

durations. Dermal risks were not assessed since a dermal hazard was not identified.

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

following scenarios: 

 Mixing/Loading liquid formulation for aerial, airblast, and application; 

 Applying sprays with aerial, airblast, and handheld equipment; 

 Flagging for aerial applications; and 

 Mixing/Loading/Applying sprays using mechanically pressurized handgun. 

Results are presented for “baseline,” defined as a single layer of clothing consisting of a long 

sleeved shirt, long pants, shoes plus socks, no protective gloves, and no respirator, as well as 

baseline with various levels of PPE as necessary (e.g., gloves, respirator, etc). Fenazaquin 

applicators and other handlers must wear long-sleeved shirts, long pants, chemical resistant 

gloves, shoes, and socks. For those mixing/loading/applying with a high-pressure handwand, 

coveralls must also be worn. 

Short- and intermediate-term risk estimates for occupational handlers are included in Table 9.1.1. 

All handler scenarios resulted in MOEs greater than the LOC (MOEs ≥ 100) for baseline 

inhalation exposures, and therefore are not of concern. The short-term occupational handler 

inhalation MOEs ranged from 4,700 to 520,000.
Fenazaquin Human Health Risk Assessment DP No. 391819

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1 Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (March 2014); Level of mitigation: Baseline, except for aerial application which is baseline with Eng. 

Controls.

2 Based on proposed label (Reg. No. 10163-GEE).

3 Exposure Science Advisory Council Policy #9.1.

4 Inhalation Dose = Inhalation Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled Daily (A or gal/day) ÷ BW (80 

kg).

5 Inhalation MOE = Inhalation NOAEL (5 mg/kg/day) ÷ Inhalation Dose (mg/kg/day).

Table 9.1.1: Occupational Handler Non-Cancer Exposure and Risk Estimates for Fenazaquin.

Exposure Scenario Crop or Target Level of Concern

Inhalation Unit 

Exposure (μg/lb ai)1 Maximum

Application Rate2

Area Treated or 

Amount 

Handled Daily3

Inhalation

Baseline (no 

respirator)

Dose 

(mg/kg/day)4 MOE5

Mixer/Loader

Mixing/Loading Liquids for Aerial 

Application Almonds and 

Cherries 100 0.219 0.45 lb ai/A

350 acres 0.00043 12,000

Mixing/Loading Liquids for Airblast 

Application 40 acres 0.000049 100,000

Applicator

Aerial Application Almonds and 

Cherries 100

0.0049

0.45 lb ai/A

350 acres 0.0000097 520,000

Airblast Application 4.71 40 acres 0.0011 4,700

Flagger

Flagging for Aerial Application Almonds and 

Cherries 100 0.35 0.45 lb ai/A 350 acres 0.00069 7,300

Mixer/Loader/Applicator

Mixing/Loading/Applying using 

Mechanically Pressurized Handgun

Almonds and 

Cherries 100 3.9 0.0090 lb ai/gal 1000 gal 0.00044 11,000
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9.2 Short-/Intermediate-Term Post-Application Risk

9.2.1 Dermal Post-application Risk

There is the potential for occupational dermal post-application exposure for individuals exposed 

as a result of being in an environment that has been previously treated with fenazaquin. 

However, since there is no adverse systemic hazard via the dermal route of exposure, an 

occupational post-application assessment has not been conducted. 

Restricted Entry Interval

The REI specified on the proposed label is based on the acute toxicity of fenazaquin. Fenazaquin

is classified as Toxicity Category IV via the dermal route and Toxicity Category IV for skin 

irritation potential. It is classified as a skin sensitizer. Under 40 CFR 156.208(c)(2)(iii), ai’s 

classified as Acute III or IV for acute dermal, eye irritation and primary skin irritation are 

assigned a 12-hour REI. Therefore, the [156 subpart K] Worker Protection Statement interim 

REI of 12 hours is adequate to protect agricultural workers from post-application exposures to 

fenazaquin. 

9.2.2 Inhalation Post-application Risk

There are multiple potential sources of post-application inhalation exposure to individuals 

performing post-application activities in previously treated fields. These potential sources 

include volatilization of pesticides and resuspension of dusts and/or particulates that contain 

pesticides. The agency sought expert advice and input on issues related to volatilization of 

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

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

(http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The agency has 

evaluated the SAP report and has developed a Volatilization Screening Tool and a subsequent 

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

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

required for fenazaquin.

In addition, the Agency is continuing to evaluate the available post-application inhalation 

exposure data generated by the Agricultural Reentry Task Force. Given these two efforts, the 

Agency will continue to identify the need for and, subsequently, the way to incorporate 

occupational post-application inhalation exposure into the agency's risk assessments.

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

performed, an inhalation exposure assessment was performed for occupational/commercial 

handlers. Handler exposure resulting from application of pesticides outdoors is likely to result in 

higher exposure than post-application exposure. Therefore, it is expected that these handler 

inhalation exposure estimates would be protective of most occupational post-application 

inhalation exposure scenarios.
Fenazaquin Human Health Risk Assessment DP No. 391819

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Furthermore, inhalation exposure during dusty mechanical activities such as shaking and 

mechanical harvesting is another potential source of post-application inhalation 

exposure. However, the airblast applicator scenario is believed to represent a reasonable worst 

case surrogate estimate of post-application inhalation exposure during these dusty mechanical 

harvesting activities. The non-cancer inhalation risk estimate for commercial airblast application 

is not of concern (i.e., MOE > 100).

10.0 References

Funk, S., 07/25/12, DP381810, 401360, Fenazaquin. Petition for the Establishment of 

Permanent Tolerances and Registration for Use on Alfalfa, Avocado, Berry Fruit Group 13, 

Citrus Fruits Group 10, Field Corn, Sweet Corn, Cotton, Cucurbit Vegetables Group 9, EdiblePodded Legume Vegetables Subgroup 6-A, Succulent Shelled Pea and Bean Subgroup 6B 

(Except Soybean), Dry Bean and Pea Subgroup 6-C, Fruiting Vegetables (Except Cucurbits) 

Group 8, Grapes, Hops, Mint, Pome Fruits Group 11, Stone Fruits Group 12, Strawberry, and 

Tree Nuts Group 14. Summary of Analytical Chemistry and Residue Data.

Hebert, J., DP394030, 03/8/12, Drinking Water Assessment to Support First Fenazaquin (4-tertbutylphenethyl quinazolin-4-yl ether) Use on Food Crops.

Negrón-Encarnación ,I., 04/18/12, DP397773, Fenazaquin. Report of the Residues of Concern 

Knowledgebase Subcommittee (ROCKS). 

Rury, K., 08/XX/14, DP391813, FENAZAQUIN: Occupational Exposure Assessment for 

Proposed Use on Almonds and Cherries, and a Re-Evaluation of Existing Residential Uses. 

Walls, C., 06/16/14, DP391808, Fenazaquin: Acute and Chronic Aggregate Dietary Exposure 

and Risk Assessments for the Section 3 Registration Action on Almonds and Cherries. 
Fenazaquin Human Health Risk Assessment DP No. 391819

Page 30 of 45

Appendix A. Toxicology Profile 

A.1 Toxicology Data Requirements

The requirements (40 CFR 158.500) for food uses are in the table below. Use of the new 

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

Table A.1: Toxicology Data Requirements

Guideline Study Type Required Submitted Satisfied

870.1100 Acute Oral Toxicity Yes Yes Yes

870.1200 Acute Dermal Toxicity Yes Yes Yes

870.1300 Acute Inhalation Toxicity Yes Yes Yes

870.2400 Acute Eye Irritation Yes Yes Yes

870.2500 Acute Dermal Irritation Yes Yes Yes

870.2600 Skin Sensitization Yes Yes Yes

870.3100 90-Day Oral Toxicity in Rodents Yes Yes Yes

870.3150 90-Day Oral Toxicity in Non-Rodents Yes Yes Yes

870.3200 21/28-Day Dermal Toxicity Yes Yes Yes

870.3250 90-Day Dermal Toxicity CR No NA

870.3465 90-Day Inhalation Toxicity CR No Yes2

870.3700 Prenatal Developmental Toxicity Study (Rat) Yes Yes Yes

Prenatal Developmental Toxicity Study (Rabbit) Yes Yes No

870.3800 Reproduction and Fertility Effects Yes Yes Yes

870.4100 Chronic Toxicity (Rodent) Yes Yes Yes

870.4200 Carcinogenicity (Rat) Yes Yes NA

Carcinogenicity (Mouse) Yes Yes Yes

870.5100 Bacterial Reverse Mutation Test Yes Yes Yes

870.5300

870.5375

in vitro Mammalian Cell Gene Mutation Test

in vitro Mammalian Chromosome Aberration Test Yes1 YesYes Yes

870.5385

870.5395

Mammalian Bone Marrow Chromosomal Aberration Test

Mammalian Erythrocyte Micronucleus Test Yes1 NoYes Yes

870.6100 Delayed Neurotoxicity of Organophosphorus Substances (Acute, Hen) CR No NA

Delayed Neurotoxicity of Organophosphorus Substances (28-Day, Hen) CR No NA

870.6200 Neurotoxicity Screening Battery (Acute, Rat) Yes Yes Yes

Neurotoxicity Screening Battery (90-Day, Rat) Yes No Yes2

870.6300 Developmental Neurotoxicity Study CR No NA

870.7200 Companion Animal Safety CR No NA

870.7485 Metabolism and Pharmacokinetics Yes Yes Yes

870.7600 Dermal Penetration CR No NA

870.7800 Immunotoxicity Yes Yes Yes

CR: Conditionally Required

NA: Not Applicable

1 Either guideline study type may be used to satisfy the data requirement (e.g., 870.5300 or 870.5375)

2 Requirement waived by HASPOC on 10 April 2014 – TXR 0056942
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A.2 Toxicity Profiles

Table A.2.1: Acute Toxicity Profile

Guideline Study Type MRID Results Toxicity Category

870.1100 Acute Oral Toxicity 46684003 LD50 = 134/138 mg/kg II

870.1200 Acute Dermal Toxicity 47097627 LD50 > 5000 mg/kg IV

870.1300 Acute Inhalation Toxicity 47097628 LC50 = 1.96 mg/L III

870.2400 Acute Eye Irritation 47097629 Minimal irritation III

870.2500 Acute Dermal Irritation 47097627 Not irritating IV

870.2600 Dermal Sensitization 47097630

Positive (unacceptable study): in lieu of an 

acceptable dermal sensitization study 

demonstrating otherwise, TRB/RD recommends 

this chemical be labeled a dermal sensitizer.

---

Table A.2.2: Subchronic, Chronic, and Other Toxicity Profiles

Guideline Study Type MRID (year) / Doses / Classification Results

870.3100 90-Day Oral 

Toxicity in 

Rodents (Rat)

45029904 (1992)

Dietary Concentration (ppm):

0, 15, 45, 150, 450

Dose (mg/kg/day):

M: 0, 1.0, 3.0, 9.6, 28.7

F: 0, 1.2, 3.5, 11.5, 33.0

Acceptable / Guideline

NOAEL (mg/kg/day): M = 9.6 F = 11.5

LOAEL (mg/kg/day): M = 28.7 F = 33.0

Based on decreased body weight and food 

consumption.

45029905 (1992)

Gavage Dose (mg/kg/day):

M: 0, 1, 3, 10, 30

F: 0, 1, 3, 10, 30

Acceptable / Guideline

NOAEL (mg/kg/day): M = 10 F = 10

LOAEL (mg/kg/day): M = 30 F = 30

Based on decreased body weight and food 

consumption/efficiency.

90-Day Oral 

Toxicity in 

Rodents 

(Hamster)

45029903 (1992)

Gavage Dose (mg/kg/day):

M: 0, 5, 25, 75, 150

F: 0, 5, 25, 50, 100

Acceptable / Guideline

NOAEL (mg/kg/day): M = 25 F = 25

LOAEL (mg/kg/day): M = 75 F = 50

M: Based on decreased body weight, reduced testes 

and prostate weights, and testicular 

hypospermatogenesis

F: Based on decreased body weight

870.3150 90-Day Oral 

Toxicity in NonRodents (Dog)

45029901 (1992) 

Dietary Concentration (ppm):

Information was not available

Dose (mg/kg/day):

M: 0, 1, 5, 15

F: 0, 1, 5, 15

Acceptable / Guideline

NOAEL (mg/kg/day): M = 5 F = 5

LOAEL (mg/kg/day): M = 15 F = 15

Based on decreased body weight and food 

consumption/efficiency.

870.3200 21/28-Day

Dermal Toxicity 

(Rabbit)

48143805 (1992)

Dose (mg/kg/day):

M: 0, 100, 315, 1000

F: 0, 100, 315, 1000

Acceptable / Non-Guideline

Systemic

NOAEL (mg/kg/day): M = 1000 F = 1000

LOAEL (mg/kg/day): M > 1000 F > 1000

870.3465 90-Day 

Inhalation 

Toxicity

Study was not submitted Study requirement waived by HASPOC 

TXR 0056942 (10 April 2014)

83-3

870.3700

Prenatal 

Developmental 

Toxicity Study 

(Rat)

45029911 (1989) 

Gavage Dose (mg/kg/day):

F: 0, 3, 10, 40

Acceptable / Guideline

Maternal

NOAEL (mg/kg/day) = 10

LOAEL (mg/kg/day) = 40

Based on findings (as early as GD 6-9) of 

decreased food intake and food efficiency.

Developmental

NOAEL (mg/kg/day) = 40

LOAEL (mg/kg/day) > 40
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Table A.2.2: Subchronic, Chronic, and Other Toxicity Profiles

Guideline Study Type MRID (year) / Doses / Classification Results

Prenatal 

Developmental 

Toxicity Study 

(Rabbit)

45029912 (1990) 

Gavage Dose (mg/kg/day):

F: 0, 3, 13, 60

Acceptable / Non-Guideline

The 60 mg/kg/day dose was excluded 

due to an unusually high number of 

mortalities that were not treatment 

related.

Maternal

NOAEL (mg/kg/day) = 13

LOAEL (mg/kg/day) > 13

Developmental

NOAEL (mg/kg/day) = 13

LOAEL (mg/kg/day) > 13

83-4

870.3800

Reproduction and 

Fertility Effects 

(Rat)

46684001 (1991) 

Gavage Dose (mg/kg/day):

M: 0, 1, 5, 25

F: 0, 1, 5, 25

Acceptable / Guideline

Parental

NOAEL (mg/kg/day) = 5

LOAEL (mg/kg/day) = 25

Based on excessive salivation and decreased body 

weight and food intake.

Reproductive

NOAEL (mg/kg/day) = 25

LOAEL (mg/kg/day) > 25

Offspring

NOAEL (mg/kg/day) = 5

LOAEL (mg/kg/day) = 25

Based on decreased weight gain during lactation.

83-1

870.4100

Chronic Toxicity 

(Dog)

45029906 (1993)

Dietary Concentration (ppm):

Information was not available

Dose (mg/kg/day):

M: 0, 1, 5, 12

F: 0, 1, 5, 12

Acceptable / Guideline

NOAEL (mg/kg/day): M = 5 F = 5

LOAEL (mg/kg/day): M = 12 F = 12

Based on decreased body weight and food 

consumption, and food efficiency.

870.4200 Carcinogenicity 

(Hamster)

45029913 (1992)

Gavage Dose (mg/kg/day):

M: 0, 2, 15, 30

F: 0, 2, 15, 35

Acceptable / Guideline

The Registrant’s justification for using 

hamsters can be found in MRID 

44742910

NOAEL (mg/kg/day): M = 2 F = 15

LOAEL (mg/kg/day): M = 15 F = 35

M: Based on decreased body weight gain

F: Based on decreased body weight 

No evidence of carcinogenicity

870.4300 Combined 

Chronic Toxicity/

Carcinogenicity 

(Rat)

45029907 (1992)

Dietary Concentration (ppm):

0, 10, 100, 200, 400 (M)

450 (F)

Dose (mg/kg/day):

M: 0, 0.46, 4.5, 9.2, 18.3

F: 0, 0.57, 5.7, 11.5, 25.9

Acceptable / Guideline

NOAEL (mg/kg/day): M = 9.2 F = 11.5

LOAEL (mg/kg/day): M = 18.3 F = 25.9

Based on decreased body weight, food 

consumption, and food efficiency.

No evidence of carcinogenicity

870.5100 Bacterial Reverse 

Mutation Test

(Salmonella 

typhimurium)

44742909 (1989)

Applied Dose (μg/plate):

S9: 0, 187.5, 375, 750, 1500, 3000

Acceptable / Guideline 

±S9: Negative up to 3000 μg/mL in the absence of 

cytotoxicity with precipitation above this 

concentration.

870.5300 in vitro

Mammalian Cell 

Gene Mutation 

Test

(Mouse 

Lymphoma 

Cells)

44742908 (1989)

Applied Dose (μg/mL):

-S9: 0, 0.05, 0.1, 0.5, 1.0, 2.5, 5.0, 10.0,

20.0

+S9: 0, 0.5, 1.0, 2.0, 4.0, 6.0, 8.0, 10.0

12.0

Acceptable / Guideline

-S9: Negative, severely cytotoxic at concentrations 

up to10 μg/mL

+S9: Positive at concentrations (up to 12 μg/mL) 

that were severely cytotoxic (10-20% survival)
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Table A.2.2: Subchronic, Chronic, and Other Toxicity Profiles

Guideline Study Type MRID (year) / Doses / Classification Results

870.5375 in vitro

Mammalian 

Chromosome 

Aberration Test

(Chinese Hamster 

Ovary cells)

44742907 (1989)

Applied Dose (μg/mL):

-S9: 0, 0.1, 0.5, 1.0

+S9: 0, 40 50, 60

Acceptable / Guideline

± S9: Negative for clastogenic/aneugenic activity 

up to concentrations that reduced cell survival by 

≈50% (1 μg/mL-S9; 60 μg/mL+S9). Compound 

precipitation was evident at levels ≥ 24 μg/mL +/-

S9.

870.5395 Mammalian 

Erythrocyte 

Micronucleus Test

(Mouse)

44742904 (1989)

Gavage Dose (mg/kg):

M: 0, 400, 800, 1600

F: 0, 400, 800, 1200

Acceptable / Guideline

Negative for clastogenic/aneugenic activity in 

mouse bone marrow up to the highest dose tested in 

males/females (1600/1200 mg/kg, repeated on two 

days). 

In a preliminary study, the median lethal doses 

(MLD) were 3191/ 2430 mg/kg (M/F).

870.5550 Unscheduled 

DNA Synthesis

in Mammalian 

Cells in Culture

(Rat

Hepatocytes)

44742906 (1989)

Dose (μg/mL):

-S9: 0, 0.001, 0.005, 0.01,

0.05, 0.1, 0.5, 1.0,

5.0

Acceptable / Guideline

Negative up to cytotoxic concentrations (≥0.5 to 

1.0 μg/mL).

--- Unscheduled 

DNA Synthesis

(in vitro and in 

vivo)

45029908 (1989)

Dose (μg/mL):

-S9: 0, 180, 600

Acceptable / Non-Guideline

Negative for DNA damage and repair in this in 

vivo/in vitro test system up to the maximum 

tolerated dose (600 mg/kg). 

870.5915 in vivo Sister 

Chromatid 

Exchange Assay

(Mouse)

44742905 (1989)

Gavage Dose (mg/kg):

M: 0, 500, 1000, 2000

Unacceptable / Guideline 

Unacceptable due to inadequate number 

of test animals (each data point had 3 

males which is lower than the guideline 

recommended 5/sex/dose)

Negative in this cytogenetic assay (no increase in 

SCE) of bone marrow from male CD-1 mice treated 

with doses up to levels that produced death (2000 

mg/kg).

870.6200 Neurotoxicity 

Screening Battery

(Acute Rat)

48814001 (2012)

Gavage Dose (mg/kg):

M: 0, 20, 65, 130

F: 0, 20, 60, 120

Acceptable / Guideline

NOAEL (mg/kg/day): M = 20 F = 20

LOAEL (mg/kg/day): M = 65 F = 60

Based on mild dehydration in females.

Neurotoxicity 

Screening Battery

(Subchronic Rat)

Study has not been submitted Study requirement waived by HASPOC

TXR 0056942 (10 April 2014)

870.7485 Metabolism and 

Pharmacokinetics 

(Rat)

44742901 (1992)

Gavage Dose (mg/kg):

Single: 1, 30

Repeated: 1

Acceptable / Guideline

Absorption

Absorption was determined to be 65.09% of the 

administered dose (AD). The urine contained 

3.75% AD. 

Distribution

Fenazaquin residues were found in low levels 

throughout the rat with detectable levels in a broad 

range of organs (i.e. brain, kidneys, and liver) as 

well as in the residual carcass. The residue levels

in the rat organs and tissues were <0.04% AD. The 

rat carcass without the previously mentioned organs 

contained ≤1.6% AD.
Fenazaquin Human Health Risk Assessment DP No. 391819

Page 34 of 45

Table A.2.2: Subchronic, Chronic, and Other Toxicity Profiles

Guideline Study Type MRID (year) / Doses / Classification Results

48907401 (2012) – Tier 2 Study

Gavage Dose (mg/kg):

Single: 1

Acceptable / Guideline

Metabolism

Non-metabolized fenazaquin was higher in feces 

(1.0-15.0% AD) than in urine (<0.5% AD) and 

some of the major metabolites were identified 

including AN-1 (urine) in addition to the fecal 

metabolites F-1, F-2 and F-3. The metabolic 

pathway of fenazaquin involved cleavage of the 

ether bond, resulting in the formation of the 

respective alcohol (4-OH quinazoline metabolite) 

and carboxyl acid (AN-1) derivatives. Other 

biotransformation reactions included oxidation of 

one of the methyl groups on the alkyl side chain to 

produce either an alcohol (F-1) or carboxylic acid 

(F-2) metabolites. Finally, hydroxylation at the Oether alkyl moiety of F-1 or the 2-position of the 

quinazoline ring of F-2 resulted in F-1A and F-3 

metabolites, respectively.

Elimination

The majority (89.5-107.7%) of elimination in the 

rat occurred within 168 hours. There was no 

radiolabel in the expired air and no evidence for 

bioaccumulation. Based on excretion and tissue 

residue data, bioavailability is conservatively 

estimated at about 20% of an administered dose.

870.7600 in vitro 

Dermal 

Penetration 

(Human & Rat)

48012905 (2007)

Study is not acceptable without an in 

vivo guideline OPPTS 870.7600 study 

submission

Preliminary review of the study indicates a dermal 

absorption of 0.48-7.33%.

870.7800 Immunotoxicity

(Rat)

48459503 (2011)

Gavage Dose (mg/kg/day):

F: 0, 15, 30, 37.5/45

Acceptable / Non-Guideline

Systemic Toxicity

NOAEL (mg/kg/day) = 15

LOAEL (mg/kg/day) = 30

Based on clinical signs (general ataxia/hypoactivity) (also seen after a single dose).

Immunotoxicity

NOAEL (mg/kg/day) = 37.5

LOAEL (mg/kg/day) > 37.5

NA Potential of XDE436 Analogues to 

Induce Hepatic 

Hypertrophy and 

Peroxisome AcylCoA Oxidase 

Activity (Mouse)

44742903 (1993)

Acceptable / Non-Guideline

Fenazaquin and several of its analogs (with varying 

susceptibilities to metabolism of the ether bond or 

the alkylbenzene substituents) were assessed for 

their ability to increase liver peroxisomal fatty acylCoA oxidase (FAO, a marker of peroxisomal 

proliferation) and relative liver weight in groups of 

five CD-1 female mice. The FAO peroxisomal 

activity data indicate that oxidation of the t-butyl 

substituent on the alkylbenzene moiety (to the 

corresponding carboxylic acid) of fenazaquin and 

related compounds appears to be the critical step 

for hepatocellular peroxisome proliferation.
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Appendix B. Proposed Metabolic Pathways for Fenazaquin (EL-436) in the Rat
Fenazaquin Human Health Risk Assessment DP No. 391819

Page 36 of 45

Appendix C. Physical/Chemical Properties

Table C1. Physicochemical Properties of Fenazaquin.

Parameter Value Reference

Melting point/range 77.5-80oC Evaluation on Fenazaquin, 

Issue No. 150, Pesticides 

Safety Directorate, Depart. 

for Environment, Food, 

and Rural Affairs, U.K., 

March 1996

pH Not determined due to low solubility

Relative Density 1.16 at 21oC

Water solubility (20°C) 0.102 mg/L at pH 5 & 7

0.135 mg/L at pH 9

Solvent solubility

(g/L at 23oC)

acetonitrile 33-50 acetone 400-500

n-chlorobutane >500 chloroform >500

dichloromethane >600 ethyl acetate 400-500 

dimethylformamide 300-400 ethylene glycol <5

hexane 33-50 isopropanol 50-100

methanol 50-100 toluene >500

N-methyl-2-pyrrolidone >500

Vapor pressure (25oC) 1.9 x 10-5 Pa; 1.4 x 10-7 mmHg

16 x 10-5 Pa

35 X 10-5 Pa

Dissociation constant, pKa 2.44

Octanol/water partition 

coefficient, Log(KOW)

5.71 at 25oC; 5.51 at 20oC

UV/visible absorption 

spectrum

Amax 215 nm

є = 41,588 L mol-1cm-1
Fenazaquin Human Health Risk Assessment DP No. 391819

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Appendix D. Structure of Fenazaquin and its major metabolites/degradates

Summary of Metabolites and Degradates

Chemical Name (other names 

in parentheses) and Structure

Matrix Percent TRR (PPM)1

Matrices - Major Residue 

(>10% TRR)

Matrices - Minor Residue 

(<10% TRR)

Fenazaquin Apple (30% 

mature)

(7 DAT)

66.4 (0.363) P

76.0 (0.461) Q

Apple (30% 

mature)

(28 DAT)

48.0 (0.070) P

39.7 (0.085) Q

Orange

(63 DAT)

65.5 (0.295) P

55.4 (0.500)Q

Grapes

(28 DAT)

63.0 (0.939) P

46.4 (1.22) Q

Grapes

(49 DAT)

39.1 (0.14) P

26.7 (0.662) Q

Corn grain

(20 DAT)

23.1 (0.003) Q

Not analyzed P

Corn stover

(20 DAT)

48.4 (2.95) Q

29.8 (1.98) P

Radish root 

(rotational) 

30 (0.031) Q 30 day PBI 15 (0.007) Q 120 day PBI

27 (0.026) P 16 (0.009) P

Lettuce immature

(rotational 30 day 

PBI)

8.0 (0.004) Q

7.3 (0.004) P

Wheat straw 

(rotational 30 day 

PBI)

1.7 (0.002) Q

0.8 (0.002) P

Muscle (Goat) N/D P

Not analyzed Q

Fat (Goat) 83.0 (0.073) Q

77.3 (0.085) Q

Kidney (Goat) N/D P and Q

Liver (Goat) N/D P and Q

Milk (Goat) 15.4 (0.004) Q

47.1 (0.016) P

Muscle, thigh 

(Chicken)

68.8 (0.011) P 5.0 (0.003) Q

Fat, subcutaneous 

(Chicken)

83.2 (0.134) Q

88.8 (0.159) P

Fat, omental 

(Chicken)

94.9 (0.147) Q

89.2 (0.156) P

Liver (Chicken) 4.6 (0.004) Q

N/D P

Eggs (Chicken) 13.0 (0.003) P 2.1 (0.003) Q

Rat 1 – 21% of residue in feces

Water Major residue

N N

O
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Summary of Metabolites and Degradates

Chemical Name (other names 

in parentheses) and Structure

Matrix Percent TRR (PPM)1

Matrices - Major Residue 

(>10% TRR)

Matrices - Minor Residue 

(<10% TRR)

Fenazaquin Dimer Apple (30% 

mature)

(7 DAT)

24.6 (0.135) P

10.1 (0.061) Q

Apple (30% 

mature)

(28 DAT)

27.4 (0.040) P

19.4 (0.041) Q

Grapes

(28 DAT)

N/D P and Q

Corn grain

(20 DAT)

7.7 (0.001) Q

Not analyzed P

Corn stover

(20 DAT)

19.8 (1.20) Q

54.3 (3.61) P

Goat Tissues – not found

Chicken Tissues – not found

Rat Not found

Water Not found

2-Methyl-2-{4-[2-(quinazolin4-yloxy)-ethyl]-phenyl}-

propan-1-ol

(Metabolite F1)

(Metabolite C)

Apple (30% 

mature)

(7 DAT)

1.0 (0.005) P [or metabolite L]

N/D Q

Apple (30% 

mature)

(28 DAT)

3.3 (0.005) P [or metabolite L]

0.4 (0.001) Q

Grapes

(28 DAT)

9.1 (0.136) P

4.3 (0.112) Q

Grapes

(49 DAT)

12.9 (0.046) P

3.3 (0.062) Q

Goat Tissues – not found

Chicken Tissues – not found

Rat 5 – 9.4% residue in feces

Water Not found

Rat 16 – 23% of TRR in feces

N

ON

N

N

O

N N

O

O
Fenazaquin Human Health Risk Assessment DP No. 391819

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Summary of Metabolites and Degradates

Chemical Name (other names 

in parentheses) and Structure

Matrix Percent TRR (PPM)1

Matrices - Major Residue 

(>10% TRR)

Matrices - Minor Residue 

(<10% TRR)

2-Methyl-2-(4-(2-((4-

quinazolinyl)oxy)ethyl)phenyl

)-propionic acid.

(Metabolite 5) 

(Metabolite F2)

Water Identified as present

(Metabolite D)

(M29)

(Metabolite F3)

(Metabolite 2 in the drinking 

water memo)

2-(4-{2-[(2-

hydroxyquinazolin-4-

yl)oxy]ethyl}phenyl)-2-

methylpropanoic acid

2-Methyl-2-(4-{2-[(2-oxo-1,2-

dihydroquinazolin-4-

yl)oxy]ethyl}phenyl) 

propanoic acid

Apple 

(105 day PHI)

0.8 (<0.001) Q

Corn stover 

(20 DAT)

0.5 (0.033) Q

N/D P

Radish root (30 

day PBI)

3.8(0.004) Q

3.2 (0.003) P

Muscle (Goat) 20.0 (0.005) P

Not analyzed Q

Fat (Goat) 0.9 (0.001) P

N/D Q

Kidney (Goat) 28.6 (0.010) Q

25.3 (0.023) P

Liver (Goat) 13.7 (0.054) Q

14.9 (0.106) P

Milk (Goat) 1.8 (0.001) Q

2.9 (0.001) P

Liver (Chicken) 7.0 (0.003) P

N/D Q

Eggs (Chicken) 13.0 (0.003) P 1.4 (0.002) Q

Rat 6.5 – 12.5% of TRR in rat 

feces

4(2-(4(1,1dimethylethyl)-

phenyl)ethoxy)quinazolone

Orange 

(191 day PHI)

8.1 (0.029) P

4.9 (0.016) Q

Corn stover

(20 DAT)

1.2 (0.073) Q

0.5 (0.030) P

N

N

O

C

H2

C

H2

C CH3

CH3

COOH

N N

O

CH3

CH3 OH HOOC

N

N

O

C

H2

C

H2

C CH3

CH3

COOH

O
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Summary of Metabolites and Degradates

Chemical Name (other names 

in parentheses) and Structure

Matrix Percent TRR (PPM)1

Matrices - Major Residue 

(>10% TRR)

Matrices - Minor Residue 

(<10% TRR)

4-[2-(4-tert-butyl-phenyl)-

ethoxy]-quinazolin-2-ol

2-Oxy-fenazaquin

2-Hydroxy-fenazaquin

(Metabolite F)

(Metabolite 1)

Radish root

(rotational, 30 day 

PBI)

3.8 (0.004) Q

4.2 (0.004) P

Radish top 

(rotational, 30 day 

PBI)

3.3 (0.001) Q

Wheat straw 

(rotational, 30 day 

PBI)

0.9 (0.001) Q

0.4 (0.001) P

Fat (goat) 1.1 (0.001) Q

0.9 (0.001)

Liver (goat) Previously reported at 4 – 10% 

TRR in a marginal study.

Rat Not found, but implied by 

oxidative metabolism and 

presence of F3 (‘fenazaquin 

acid’) in feces.

Water 8.1% of applied chemical

2-(4-(1,1-dimethyl)-phenyl)ethyl2-(formylaminobenzoate)

1-(4-Tert-butylphenyl)-2-

(quinazolin-4-yloxy)ethanone

(Metabolite H)

(Metabolite 4)

Grapes (76 DAT) 2.7 (0.028)P

N/D Q

Water Present but not quantified

Goat Not found

Chicken Not found

Rat Not found

Apple (30% 

mature)

(7 DAT)

N/D P

1.9 (0.012) Q

N/D P

N

H

N

O

C

H2

C

H2

C CH3

CH3

CH3

O

N

H

C

H

O

O

C

H2

C

H2

C CH3

CH3

CH3

O

N N

O

H C

3

CH

3

CH

3

OH
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Summary of Metabolites and Degradates

Chemical Name (other names 

in parentheses) and Structure

Matrix Percent TRR (PPM)1

Matrices - Major Residue 

(>10% TRR)

Matrices - Minor Residue 

(<10% TRR)

Dihydroxyquinazoline

(Metabolite I)

And its tautomer

Quinazolindione or

Benzoyleneurea

Apple (30% 

mature)

(28 DAT)

4.4 (0.009) Q

Orange N/D

Grapes

(28 DAT)

3.8 (0.099) Q

Grapes

(49 DAT)

4.1 (0.101) Q

Grapes

(76 DAT)

26.2 (0.248) Q, including 

14% from base hydrolysis.

Muscle, thigh 

(Chicken)

63.3 (0.038) Q

Fat, subcutaneous 

(Chicken)

14.9 (0.024) Q

Fat, omental

(Chicken)

3.2 (0.005) Q

Liver (Chicken) 52.9 (0.046) Q

Eggs (Chicken) 82.4 (0.117) Q

Goat Not found

Rat Not found

Water Identified – amount not 

reported

N

N

OH

OH
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Summary of Metabolites and Degradates

Chemical Name (other names 

in parentheses) and Structure

Matrix Percent TRR (PPM)1

Matrices - Major Residue 

(>10% TRR)

Matrices - Minor Residue 

(<10% TRR)

4-Hydroxyquinazoline

4-Quinazolinol

(Metabolite J)

And its tautomer

Quinazolidinone

Apple (30% 

mature)

(7 DAT)

0.4 (0.003) Q

Apple (30% 

mature)

(28 DAT)

3.2 (0.007) Q

Orange N/D

Grapes

(49 DAT)

1.6 (0.040) Q

Corn stover

(20 DAT)

6.9 (0.419) Q

Radish root (30 

day PBI)

8.7 (0.009) Q

Radish top (30 

day PBI)

3.3 (0.001) Q

Lettuce immature

(rotational 30 day 

PBI)

4.0 (0.002) Q

Wheat straw 

(rotational 30 day 

PBI)

4.3 (0.005) Q

Wheat hay 

(rotational 30 day 

PBI)

8.0 (0.010) Q

Wheat forage 

(rotational 30 day 

PBI)

8.1 (0003) Q

Kidney (goat) 5.7 (0.002) Q

Liver (goat) 1.9 (0.007) Q

Milk (goat) 23.1 (0.006) Q

Rat Minor component of feces 

reported in the proposed 

metabolic scheme

N

N

OH
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Summary of Metabolites and Degradates

Chemical Name (other names 

in parentheses) and Structure

Matrix Percent TRR (PPM)1

Matrices - Major Residue 

(>10% TRR)

Matrices - Minor Residue 

(<10% TRR)

Water Minor to major depending 

upon conditions

2-(4-(2-hydroxyethyl)phenyl)-

2-methyl propanoic acid 

(Metabolite K)

Grapes

(76 DAT)

4.1 (0.043) P

Tertiarybutylphenyl ethanol or

4-(1,1-

Dimethylethyl)benzeneethanol or

4-tert-butylphenethyl alcohol

(Metabolite L)

Apple

(0 DAT)

0.6 (0.005) P

Grapes

(28 DAT)

3.0 (0.08) P

Corn stover

(20 DAT)

1.8 (0.119) P

Radish root (30 

day PBI)

1.0 (0.001) P

Rat Not found, but implied present 

by general oxidative 

metabolism and presence of 

metabolite AN-1

Water Minor to major depending 

upon conditions

2-(4-carboxymethylphenyl)-2-

methylpropanoic acid

(Metabolite G)

(Metabolite M34)

Kidney (goat) 8.8 (0.008) P

Liver (goat) 15.3 (0.109) P

Rat Not found (in feces)

Water Minor identified product

HO

C

H2

C

H2

C CH3

CH3

CH3

C

H2

CH3

CH3

COOH

HOOC
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Summary of Metabolites and Degradates

Chemical Name (other names 

in parentheses) and Structure

Matrix Percent TRR (PPM)1

Matrices - Major Residue 

(>10% TRR)

Matrices - Minor Residue 

(<10% TRR)

Metabolite F1A Rat 0.8-2.6% of TRR in rat feces

Metabolite AN-1 Rat 24 – 29% TRR in rat urine

(4-tertbutylphenyl)acetic acid

(Metabolite 6)

Water Minor identified product

Rat Not found in feces, but implied 

by general oxidative 

metabolism and presence of 

metabolite AN-1

1-[3-(carboxymethyl)phenyl]-

2-methylpropionic acid

Water Minor identified product
Fenazaquin Human Health Risk Assessment DP No. 391819

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Summary of Metabolites and Degradates

Chemical Name (other names 

in parentheses) and Structure

Matrix Percent TRR (PPM)1

Matrices - Major Residue 

(>10% TRR)

Matrices - Minor Residue 

(<10% TRR)

Methyl-2-[4-(2—

oxoethyl)phenyl]-2-

methylpropanoate

Water Minor identified product

Apple; 45029914 & 45029917; 31 or 125 mg ai/L; unknown X rate; post-emergence (spray painted to fruit), early season or late 

season; 0, 7, 14, 28 and 105-day PHI (early season) or 0 and 70-day PHI (late season).

Orange; 45054401 & 44742913; 0.4 lb ai/A; 1X rate; post-emergence (foliar), early season or late season; 0, 28, 112 and 191-

day PHI (early season) or 0, 19, and 63-day PHI (late season).

Grape: 48350005 (1) Early season, 0.013 lb ai/acre, foliar, berry diameter 3 – 6 mm. Samples 0, 49, 76 DAT. (2) Late season, 

0.013 lb ai/acre, foliar; berry diameter 10 – 15 mm. Samples 0, 28 DAT.

Corn:48350008. 0.45 lb ai/acre (1X) at milk stage. Samples: corn grain and stover at 20 DAT.

Confined Rotational: 48073883. 0.45 lb ai/acre (1X) to ground. Lettuce, wheat, garden beet sowed at PBIs of 30, 120, and 365 

days.

Goat: 48350007. 0.79 mg/kg/bw/day [P} and 0.84 mg/kg bw/day [Q] or about 12 ppm based on feed; 5 

consecutive days.

Hen: 48350008. 0.97 mg/kg bw/day [Q} and 0.98 mg/kg bw/day [P{ or about 12 ppm based on feed; 7 

consecutive days.

1

Fenazaquin radiolabeled in the phenyl ring [P] or on the quinazoline ring [Q]. The label positions are depicted 

below.

* denotes position of radiolabel, uniformly labeled in 

the phenyl ring * denotes position of radiolabel, uniformly labeled in 

the phenyl ring of the quinazoline