# )



# J UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D

. C. 

### 20460



### MEMORANDUM

Date: 

### 03-DEC-2013 OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION



### SUBJECT: Quinoxyfen. 

### Human-Health Assessment Scoping Document in Support of Registration Review.

PC Code: 055459 Decision No.: 481952 Petition No.: 

### N/ A Risk Assessment Type: 

### N/ A TXRNo.: N/A MRID No.: N/A DP Barcode: D414098 Registration No.: N/ A Regulatory Action: Registration Review Scoping Document Case No.: 7037 CAS No.: 124495-18-7 40 CFR: 

### § 180.588



### George F. Kramer, Ph.D., Senior

# Che**'** ::#• 

# =-3

Jennifer R. 

### Tyler, Chemist

. 

### FROM:

Monique M. Perron, S.D., Toxicologist 

# 1'1**m"'~/J ~**  Risk Assessment Branch 1 (RAB 1) '

..,, 

# -6**~ ~**  

### Health Effects Division (HED, 7509P)

THROUGH: Charles W. Smith III, Branch Chief 

# c=**~ ~**  RAB1/HED (7509P)

## ~

TO: Katherine St. Clair, Chemical Review Manager Pesticide Re-Evaluation Division (PRD) (7508P)

Attached is HED's human-health risk assessment scoping document for quinoxyfen to support Registration Review. '

Page 1 of23Quinoxyfen Registration Review Hum an

- Health Assessment Scoping Document

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Page 2 of 23 

### Executive Summary

Quinoxyfen (5,7

- dichloro

- 4

- (4

- fluorophenoxy)quinoline) is a fungicide used for protection against powdery mildew diseases on a variety of crops. Th ere is currently one end

- use product (EP) containing quinoxyfen as the active ingredient (ai), a 22.58% ai suspension

- concentrate (SC) formulation (Quintec ® 

### , EPA Reg. No. 62719

- 375). The most recent human

- health risk assessment for quinoxyfen was complete d in 2013 (Memo, G. Kramer et al

., 20

- AUG

- 201 3 D 410691 ) in conjunction with a registration request for use on fruiting vegetables (group 8

- 10), small fruit vine climbing except fuzzy kiwifruit (subgroup 13

- 07F), and low growing berry (subgroup 13

- 07G)

. Th ere are no residential or non

- agricultural uses registered for quinoxyfen.

HED has evaluated the status of the human

- health assessments for quinoxyfen to determine whether sufficient data are available and whether any updates are needed to support Registration Review. HED has considered all available data and human

- health risk assessments for quinoxyfen with respect to its toxicity, exposure, and usage databases, and the most updated Agency science policy and risk assessment methodologies to determine the scope of work necessary to support Registration Review.

The toxicological database is adequate for Registration Review. The primary target organs af

fected by quinoxyfen are the liver and kidney. The most sensitive species was the rat. Liver effects were seen in the subchronic rat and mouse studies as well as the chronic dog study. Subchronic effects observed in rats and mice at high doses included increased liver weights, hepatocellular hypertrophy, and individual cell hepatocellular necrosis. Chronic effects observed in the dog included increased liver weights, increased alkaline phosphatase levels, and increased incidence of very slight to slight microscopic hepatic lesions. Kidney effects were only noted in the rat combined chronic/carcinogenicity study that resulted in an increased severity of chronic progressive glomerulonephropathy in males. Body

- weight decrements were noted in the rat and/o r mouse subchronic, chronic and carcinogenicity studies as well as the rabbit developmental and rat reproduction studies.

Oral rat and rabbit developmental studies showed no increased qualitative or quantitative susceptibility of offspring to quinoxyfen in utero . In the rabbit developmental toxicity study, maternal and developmental toxicity were observed at the highest dose tested (lowest

- observed adverse

- effect level; LOAEL = 200 mg/kg/day). No maternal or developmental toxicity was observed in the r at developmental study up to the limit dose. In the two

- generation rat reproduction study, no parental effects were observed up to the highest dose tested while first

generation pup weights were reduced at the same dose. In isolation, there is evidence o f quantitative susceptibility in the two

- generation reproduction study, but assessments to parental animals in this study are intentionally limited to avoid stressing dams and affecting the rearing and care of offspring. If additional evaluations had been performed on parental animals in the
two

- generation reproduction study, including histopathology and organ

- weight assessments, then it is expected that the kidney and liver effects observed in the rat subchronic oral study and in the interim (12 months) a nd final sacrifices of the rat chronic toxicity/carcinogenicity study would have been seen at the 100 mg/kg/day dose in the reproduction study. Therefore, when using a weight

- of

- evidence approach that puts the offspring findings in the two

- generation repr oduction toxicity study in context with the full toxicological database there is no concern for susceptibility to offspring since it is anticipated that parental toxicity would have been observed at the same dose.Quinoxyfen Registration Review Hum an

- Health Assessment Scoping Document

________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ _____ ___ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ __

Page 3 of 23 

### Quinoxyfen was categorized as having lo w acute toxicity via the inhalation, oral, and dermal routes (Toxicity Category III or IV). It is a mild eye irritant (Toxicity Category III) and classified as a dermal sensitizer, but not a dermal irritant.

The residue chemistry database is adequate to support current Registration Review requirements. Adequate metabolism (crops, livestock, and rotational crops), storage stability, magnitude of the residue

, and processing data are available to support the registered uses. Adequate methods are availab le for enforcement of the currently established tolerances.

The dietary

- exposure database is adequate to support current registration requirements. The last risk assessment provided chronic dietary (food and drinking water ) exposure estimates that are below HED’s level of concern (LOC) for the general U.S. population and all population subgroups ( Memo, G. Kramer, 20

- AUG

- 201 3 ; D 410693 ). C hronic dietary (food and drinking
water ) risk estimates were less than ≤8.5 % of the c hronic population

- adjusted dose (c PAD )

. Given this dietary risk assessment was performed within the past year, updating the dietary risk
assessment during Registration Review is not expected unless there are changes to current HED policies.

The residential exposure database is adequa te to support the Registration Review process for quinoxyfen. Residential exposure/risk assessments may need to be reassessed during Registration Review to address updates to HED’s exposure policies

. The occupational exposure database is adequate to supp ort the Registration Review process for quinoxyfen. The most recent occupational handler assessment covered the relevant exposure scenarios and did not result in risk estimates of concern. Revised occupational handler assessments will not be required dur ing Registration Review.

An occupational post

- application dermal assessment was not conducted previously due to the absence of short

- and intermediate

- term dermal points of departure (PODs) . A quantitative occupational post

- application assessment will no t be necessary during Registration Review. It should be noted that chemical

- specific dislodgeable foliar residue (DFR) data are available for quinoxyfen on grapes (MRID# 45360727), and are currently under review by HED. If, in the future, toxicological e ndpoints change, a dermal occupational post

- application assessment will incorporate the chemical

- specific DFR data.

The following data deficiencies were identified for quinoxyfen :

• Toxicology:

o None.

• Residue Chemistry:

o None

.

• Dietary Exposure:

o None

.

• Occupational/Residential Exposure:

o None.

EPA anticipates conducting the following risk assessment updates during Registration Review:

• Toxicology:

o None.Quinoxyfen Registration Review Hum an

- Health Assessment Scoping Document

________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ _____ ___ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ __

Page 4 of 23 

### • Residue Chemistry:

o None

.

• Dietary Exposure:

o None.

• Occupational/Residential Exposure:

o T he need for spray drift and volatilization risk assessment s for quinoxyfen will be examined during R egistration R eview

.

1.0 Introduction

Quinoxyfen is a fungicide used for protection against powdery mildew diseases on a variety of crops. There are no residential or non

- agricultural uses registered for quinoxyfen. There is currently one EP containing quinoxyfen, a 22.58% ai SC formulation (Quintec ® 

### , EPA Reg. No. 62719

- 375). The most recent human

- health risk assessment for quinoxyfen was completed in 2013 (Memo, G. Kramer et al

., 20

- AUG

- 201 3 D 410691 ) in conjunction with a registration request for use on fruiting vegetables (group 8

- 10), small fruit vine climbing except fuzzy kiwifruit (subgroup 13

- 07F), and low growing berry (subgroup 13

- 07G)

. This memo only evaluates the status of the human

- health assessments for quinoxyfen

.

2.0 Hazard Characterization/Assessment

Radiolabeled quinoxyfen was readily absorbed by rats with peak plasma concentrations occurring within 0.5

- 1.5 hours after administr ation. Within 24 hours of dosing, 68

- 85% of the dose was recovered in the excreta of all groups. Quinoxyfen was extensively metabolized in rats with major metabolites identified in the urine, bile, and feces. The major routes of elimination were through the urine and feces. Concentrations of radioactivity were detected in the kidneys, liver, ovaries, perirenal fat, gastrointestinal tract, and carcass. Generally, tissue concentrations of radioactivity were slightly lower in the males than females.

Quin oxyfen was categorized as having low acute toxicity via the inhalation, oral, and dermal routes (Toxicity Category III or IV). It is a mild eye irritant (Toxicity Category III) and classified as a dermal sensitizer, but not a dermal irritant.

The primary target organs affected by quinoxyfen are the liver and kidney. The most sensitive species was the rat. Liver effects were seen in the subchronic rat and mouse studies as well as the chronic dog study. Subchronic effects observed in rats and mice at hig h doses included increased liver weights, hepatocellular hypertrophy, and individual cell hepatocellular necrosis. Chronic effects observed in the dog included increased liver weights, increased alkaline phosphatase levels, and increased incidence of very slight to slight microscopic hepatic lesions. Kidney effects were only noted in the rat combined chronic/carcinogenicity study that resulted in an increased severity of chronic progressive glomerulonephropathy in males. Body

- weight decrements were noted in the rat and/or mouse subchronic, chronic and carcinogenicity studies as well as the rabbit developmental and rat reproduction studies.

Oral rat and rabbit developmental studies showed no increased qualitative or quantitative susceptibility of offsprin g to quinoxyfen in utero . In the rabbit developmental toxicity study, maternal and developmental toxicity were observed at the highest dose tested (LOAEL = 200 mg/kg/day). Maternal effects included inanition, clinical signs, decreased body weight and bod y

- weight gains, decreased food consumption, and increased incidence of abortion late in pregnancy. Developmental toxicity was evidenced as increased incidence of abortion late inQuinoxyfen Registration Review Hum an

- Health Assessment Scoping Document

________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ _____ ___ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ __

Page 5 of 23 

### pregnancy. No maternal or developmental toxicity was observed in the rat de velopmental study up to the limit dose of 1000 mg/kg/day. In the two

- generation rat reproduction study, no parental effects were observed up to the highest dose tested (100 mg/kg/day) while first

- generation pup weights were reduced at the same dose. In i solation, there is evidence of quantitative susceptibility in the two

- generation reproduction study, but assessments to parental animals in this study are intentionally limited to avoid stressing dams and affecting the rearing and care of offspring. If ad ditional evaluations had been performed on parental animals in the two

generation reproduction study, including histopathology and organ

- weight assessments, then it is expected that the kidney and liver effects observed in the rat subchronic oral study and in the interim (12 months) and final sacrifices of the rat chronic toxicity/carcinogenicity study would have been seen at the 100 mg/kg/day dose in the reproduction study. Therefore, when using a weight

- of

- evidence approach that puts the offspring findin gs in the two

- generation reproduction toxicity study in context with the full toxicological database

, there is no concern for susceptibility to offspring since it is anticipated that parental toxicity would have been observed at the same dose.

There is no evidence of carcinogenicity based on studies in rats or mice. Quinoxyfen did not show evidence of mutagenicity in in vitro or in vivo studies.

No evidence of neurotoxicity or neuropathology was seen in any of the submitted studies for quino xyfen.

An immunotoxicity study showed no evidence of immunotoxicity up to the highest dose tested.

Conclusions : The toxicology database is complete to support existing registrations and registration review (Attachment 2 ). No additional toxicological st udies are currently required. The endpoints from the most recent human

- health risk assessment for quinoxyfen ( G. Kramer et al

., 20

- AUG

- 201 3 D 410691 ) can be found in Attachment 3 . Given this risk assessment was performed within the past year, modification of endpoints, doses

, or safety factors is not expected during registration review unless there are changes to current HED policies.

3.0 Residue Chemistry

Permanent tolerances are established fo r residues of quinoxyfen per se [40 CFR §180.588 (a)] in/on cherries (0.30 ppm); grapes (0.60 ppm); hop, dried cones (3.0 ppm); lettuce, head (7.0 ppm); lettuce, leaf (19 ppm); pepper, bell (0.35 ppm); pepper, nonbell (1.7 ppm); strawberry (0.90 ppm); pump kin (0.30 ppm); squash, winter (0.30 ppm); and melon subgroup 9A (0.08 ppm). As indicated above, HED has recently recommended for establishment of tolerances for residues of quinoxyfen per se in/on vegetable, fruiting, group 8

- 10 ( 1.7 ppm); fruit, small v ine climbing, except fuzzy kiwifruit, subgroup 13

- 07F (2.0 ppm); and berry, low growing subgroup 13

- 07G (1.0 ppm)

. There are currently no tolerances for quinoxyfen residues in livestock commodities or for inadvertent residues in rotational crops.

Based o n acceptable cucumber, grape, sugar beet, and tomato metabolism studies, the nature of the residue in plants is adequately understood in the subject crops. Quinoxyfen was the primary residue component in all reviewed plant metabolism studies except in whe at grain and straw where Metabolite A was the predominant residue. Metabolite A was determined not to be associated with the parent quinoxyfen, or related compounds, but was characterized to be highly polar and multi

- component in nature. In cucumber and tomato, unchanged quinoxyfen remained largely on the surface of treated plants. The presence of multiple unidentified polar residuesQuinoxyfen Registration Review Hum an

- Health Assessment Scoping Document

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Page 6 of 23 

### suggests that metabolism of quinoxyfen does occur to some extent to form more polar soluble components with the incorporat ion into insoluble material. Degradates and conjugates may be incorporated into natural constituents such as lignin and cellulose. The HED Metabolism Assessment Review Committee (MARC) has determined that the residue of concern for purposes of tolerance enforcement and risk assessment is the parent compound only.

There are no livestock feed items associated with the registered crops. Therefore, no livestock metabolism studies are required to support current uses of quinoxyfen

. Adequate field trial data are available to support the use of quinoxyfen on the registered crops

. An adequate number of trials were conducted in the appropriate geographical regions using the appropriate formulation applied at the maximum use rate. These studies are also support ed by adequate storage stability data. The available processing studies for tomato and grape are adequate and indicate that separate tolerances are not required for residues in/on any of the processed fractions

. An adequate gas chromatography/mass

- selective detector (GC/MSD) method is available for enforcing tolerances (DowElanco Procedure ERC95.26); a successful petition method validation (PMV) has been completed (Memo, E. Kolbe, 5/11/06; D285350). The lowest level of method

va lidation (LLMV) was 0.01 ppm. Quinoxyfen was also successfully recovered using the QuEChERS Multiresidue Method (http://www.crl

pesticides.eu/library/docs/fv/CRLFV_Multiresidue_methods.pdf).

Dow AgroSciences submitted the results of limited rotational crop field trials for quinoxyfen on radish roots and tops, mustard greens, and on wheat grain, forage, hay, and straw conducted at a total seasonal application rate of ~0.39 lb ai/A (1X). The st udy showed that the residues of concern [quinoxyfen, 2

- oxo

- quinoxyfen, and 5,7

- dichloro

- 4

- hydroxyquinoline (DCHQ)] are each below 0.01 ppm at the 30

- day PBI and at all other PBIs that were examined. The 30

- day PBI on the product labels is thus appropriate

.

Conclusions: The residue chemistry database is adequate to support current R egistration Review data requirements. Adequate metabolism ( primary and rotational crops), storage stability, magnitude of the residue and processing data are available to supp ort the registered uses. Adequate methods are available for enforcement of the currently established tolerances.

4.0 Dietary Exposure

In 20 13

, HED conducted chronic dietary exposure analyses for all currently registered and proposed food uses of quino xyfen ( Memo, G. Kramer, 20

- AUG

- 201 3 D 410693 ). No toxic effects attributable to a single (i.e., acute) exposure to quinoxyfen have been identified; therefore, an acute dietary exposure assessment has not been conducted. The drinking water estimate from the existing /proposed U.S. uses was incorporated directly into the dietary assessment using the concentration for surface water generated by the FQPA Index Reservoir Screening Tool (FIRST). Assumptions for the chronic assessment included tolerance

- level

r esidues and 100% crop

- treated (CT) for registered and proposed uses, and Dietary Exposure Evaluation Model (DEEM) 7.81 default processing factors (where provided). A cancer dietary assessment was not conducted because quinoxyfen is classified as “not like ly to be carcinogenic to humans.” The chronic dietary risk estimates (food and drinking water) are below HED’s LOC (<100% of the cPAD) for the general U.S. population and all population subgroups. The most highly exposed population subgroup is children 1

- 2 years old with a risk estimate of 8.5% of theQuinoxyfen Registration Review Hum an

- Health Assessment Scoping Document

________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ _____ ___ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ __

Page 7 of 23 

### cPAD.

Conclusions: The dietary

- exposure database is adequate to support current R egistration Review requirements. The chronic dietary assessm ent show s dietary ( food + water ) risk estimates were ≤8.5 % of t he cPAD and were, therefore, below HED’s LOC (i.e., <100% of the cPAD)

. Given this dietary risk assessment was performed within the past year, updating the dietary risk
assessment during Registration Review is not expected unless there are changes to curr ent HED policies.

5.0 Residential Exposure

There are currently no registered uses of quinoxyfen that would result in residential exposure.

Spray Drift and Volatilization Residential exposures resulting from off

- site transport (e.g., spray drift or volatilization) may occur as a result of applications of quinoxyfen . The Agency is in the process of evaluating these types of exposures and may, as appropriate, develop policie s and procedures to identify the need for and, subsequently, the way to incorporate these post

- application exposures into the Agency's risk assessments. The need for spray drift and volatilization risk assessment s for quinoxyfen will be examined during R e gistration R eview

.

Conclusions: There are currently no registered residential uses for quinoxyfen however; t he need for spray drift and volatilization risk assessment s for quinoxyfen will be examined during R egistration R eview

.

6.0 Aggregate

- Risk Assess ment

The most recent aggregate risk assessment was performed in 2013 (Memo, G. Kramer et al

., 20

- AUG

- 201 3 D 410691 ) in conjunction with a registration request for use on fruiting vegetables (group 8

- 10), small fruit vine climbing except fuzzy kiwifruit (su bgroup 13

- 07F), and low growing berry (subgroup 13

- 07G)

. Short

- and intermediate

- term assessments, which are used to evaluate aggregate dietary and residential exposures, were not performed because there are no registered or proposed residential non

- food uses. Since there are no residential uses, the chronic aggregate risks are made up only of dietary sources (food and drinking water) and the dietary exposure analysis represents chronic aggregate exposure. Quinoxyfen is classified as “not likely to be ca rcinogenic to humans”; therefore, a cancer aggregate risk assessment was not performed. The chronic aggregate risk estimates do not exceed the HED’s LOC for the general U.S. population and all population subgroups.

Conclusions : Given this aggregate risk assessment was performed within the past year, updating the aggregate risk assessment during Registration Review is not expected unless there are changes to current HED policies.

7 .0 Occupational Exposure

Quinoxyfen is a fungicide used for protection against powdery mildew diseases on a variety of crops. The agricultural uses of quinoxyfen include artichokes, cucurbit vegetables (group 9), grapes, hops, lettuce, peppers, pumpkin, stone fruit (group 12) , and strawberries (Memos, M. Dow, 23

- APR

- 2003, D 285312; M. Dow, 21

- APR

- 2008, D351766; A. Nowotarski, 15

- JUN

2010 ) . In addition, there are pending uses on fruiting vegetables (group 8

- 10), small fruit vineQuinoxyfen Registration Review Hum an

- Health Assessment Scoping Document

________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ _____ ___ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ __

Page 8 of 23 

### climbing except fuzzy kiwifruit (subgroup 13

- 07F), and low growing berry (subgroup 13

- 07G) (Memo, G. Kramer et al

., 20

- AUG

- 201 3 D 410691 ). The only registered formulation of quinoxyfen is a SC formulation (Quintec ® 

### ; EPA Reg. No 62719

- 375), with application rates ranging from 0.0325 to 0.13 lb ai/A. Quinoxyfen can be applied using aerial or ground equi pment. Attachment 4 provides a summary of the occupational use patterns.

Based on the current uses, there is a potential for exposure to quinoxyfen in occupational scenarios from handling quinoxyfen products during the application process (i.e., mixer/loaders, applicators, and mixer/loader/applicators). In addition, there is a potential for post

- application worker exposure from entering into areas previously treated with quinoxyfen.

Occupational Handlers : There is potential for short

- and inter mediate

- term handler exposures from the current uses of quinoxyfen. There is no dermal hazard; therefore, a quantitative dermal handler assessment has not been conducted. The short

- and intermediate

- term inhalation PODs are the same; therefore, estimates for short

- term durations are protective of longer

- term inhalation exposure. Chronic exposure is not expected for the current uses. As quinoxyfen is classified as “not likely” to be carcinogenic to humans, a cancer risk assessment is not necessary. A ma rgin of exposure (MOE) ≥100 is adequate to protect occupational pesticide handlers from inhalation exposures.

Based on the current use patterns and labeling, types of equipment and techniques that can potentially be used, occupational handler exposure is expected from the following exposure scenarios: mixing/loading liquids in support of aerial, groundboom, and airblast applications; applying liquids with enclosed cockpit aerial, open

- cab groundboom, and airblast equipment; flagging to support aerial appl ications; and mixing/loading/applying liquids with mechanically

pressurized handguns. The most recent quantitative occupational handler assessment was conducted in conjunction with proposed uses on fruiting vegetables (group 8

- 10), small fruit vine climbi ng except fuzzy kiwifruit (subgroup 13

- 07F), and low growing berry (subgroup 13

- 07G) (Memo, J. Tyler, 01

- AUG

- 2013 ; D410694 )

.

No chemical

- specific data were available with which to assess potential exposure to pesticide handlers. It is the policy of HED t o use the best available data to assess handler exposure. Sources of generic handler data, used as surrogate data in the absence of chemical

- specific data, include Pesticide Handlers Exposure Database Version 1.1 (PHED 1.1), the Agricultural Handler Expos ure Task Force (AHETF) database, the Outdoor Residential Exposure Task Force (ORETF) database, or other registrant

- submitted occupational exposure studies. Some of these data are proprietary (e.g., AHETF data), and subject to the data protection provision s of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) . The standard values recommended for use in predicting handler exposure that are used in this assessment, known as “unit exposures,” are outlined in the “Occupational Pesticide Handler U nit Exposure Surrogate Reference Table a 

### ,” which, along with additional information on HED policy on use of surrogate data, including descriptions of the various sources, can be found at the Agency website b



### . In the most recent occupational handler assessm ent , risk calculations were based on maximum proposed application rates, and assuming maximum area treated per day ( Memo, J. Tyler, 01

- AUG

- 2013 ; D410694 ) . Handler's exposure and risk were calculated at baseline (long pants, a

a Available: http://www.epa.gov/opp00001/science/handler

- exposure

- table.pdf
b Available: http://www.epa.gov/pesticides/science/ha ndler

- exposure

- data.htmlQuinoxyfen Registration Review Hum an

- Health Assessment Scoping Document

________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ _____ ___ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ __

Page 9 of 23 

### long

- sleeved shirt, no chemic al

- resistant gloves, and no respirator) and with PPE when necessary (e.g., chemical

- resistant gloves, respirators, and engineering controls).

Based on existing registrations, the 01

- AUG

- 2013 assessment identified all of the anticipated occupational handle r exposure scenarios. In the 01

- AUG

- 2013 assessment, for the scenarios where baseline data are available, all inhalation risks for occupational handlers are above the LOC ( MOE ≥100 ) with baseline protection (i.e., long

- sleeve shirt, long pants, shoes, and socks)

. Only engineering control data (i.e., enclosed cockpits) are available for aerial application scenarios. All inhalation risks for occupational aerial applicators are above the LOC ( MOE ≥100 ) with baseline clothing and enclosed cockpits

. The current maximum application rate for quinoxyfen is 0.13 lb ai/A. Although the most recent handler assessment was conducted using application rates of 0.098

- 0.11 lb ai/A, the resulting inhalation MOEs were 110,000

- 9,500,000, and were well above the LOC . Therefore, the most recent handler assessment is adequate to cover all registered uses of quinoxyfen.

Occupational Post

- application : Based on the registered uses, HED has determined that there is the potential for occupational post

- application exposur es to individuals entering areas treated with quinoxyfen. However, in the absence of a short

- and intermediate

- term dermal POD, a quantitative dermal post

- application exposure assessment is not necessary to support Registration Review. Based on the Agenc y's current practices, a quantitative post

- application inhalation exposure assessment has not been performed for quinoxyfen to date. However, there are multiple potential sources of inhalation exposure to individuals performing post

- application activities in previously treated fields. These potential sources include volatilization of pesticides and re

- suspension of dusts and/or particulates that contain pesticides. The Agency sought expert advice and input on issues related to volatilization of pesticide s from its FIFRA Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on March 2, 2010 ( http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html ). The Agency is in the process of evaluating the SAP report as well as available post

- application inhalation exposure data generated by the Agricultural Reentry Task Force and may, as appropriate, develop policies and procedures, to identify the need for and, subsequently, the way to incorporate occupational post

- application inhalation exposure into the Agency's risk assessments. If new policies or procedures are put into place, the Agency may revisit the need for a quantitative occupational post

- application inhalation exposure assessment for quinoxyfen.

Conclusions : The o ccupational exposure database is adequate to support the Registration Review process for quinoxyfen. The most recent occupational handler assessment covered the relevant exposure scenarios and did not result in risk estimates of concern. Revised occupati onal handler assessments will not be required during Registration Review.

An occupational post

- application dermal assessment was not conducted previously due to the absence of a short

- and intermediate

- term dermal POD. A quantitative occupational post

ap plication assessment will not be necessary during Registration Review. It should be noted that chemical

- specific DFR data are available for quinoxyfen on grapes (MRID# 45360727), and are currently under review by HED. If, in the future, toxicological end points change, a dermal occupational post

- application assessment will incorporate the chemical

- specific DFR data.

8.0 Public Health and Pesticide Epidemiology Data

For this evaluation, both the OPP Incident Data System (IDS) and the Centers for Disease C ontrol and Prevention/National Institute for Occupational Safety and Health (CDC/NIOSH)Quinoxyfen Registration Review Hum an

- Health Assessment Scoping Document

________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ _____ ___ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ __

Page 10 of 23 

### Sentinel Event Notification System for Occupational Risk

- Pesticides (SENSOR) databases were consulted for pesticide incident data on the active ingredient quinoxyfen ( M emo, E. Evans and S. Recore

, D 414421

, 29

- AUG

- 2013 ). The purpose of the database search is to identify potential patterns in the frequency and severity of the health effects attributed to quinoxyfen exposure. For the M ain IDS, from 01

- J AN

- 200 8 to 11

- J UN

- 2013, there were no incidents reported in the database involving quinoxyfen . In A ggregate IDS , from 01

- JAN

- 200 8 to 11

- JUN

- 2013

, there was one reported incident involving q uinoxyfen

. This incident was classified as minor severity. A query of SENSOR

- Pesti cides from 1998

- 2009 identifies 11 cases, stemming from seven events, involving quinoxyfen. There were no single

- ai cases reported. All quinoxyfen cases involved multiple active ingredients. One case was high severity, one was moderate severity, and nin e were low severity. The case description for the high severity case states, “A 36 year old grape applicator reports that after turning on the air conditioner in the cab of the tractor he could smell the pesticide and became ill. He initially reported ga strointestinal, ocular, and respiratory symptoms. He sought medical c are eight days later for increasing respiratory symptoms.”

Conclusions : Based on the low frequency and generally low severity of incident cases reported for quinoxyfen in both IDS and SENSOR

- Pesticides, there does not appear to be a concern at this time that would warrant further investigation. The Agency will continue to monitor the incident information and if a concern is triggered, additional analysis will be included in the Registration Review risk assessment.

9 .0 Tolerance Assessment and International Harmonization

Codex MRLs are established for residues of quinoxyfen per se in/on cherries; hops, dry; lettuce, head; lettuce, leaf; melons, except watermelon; peppers strawbe rries, and grapes (Attachment 5)

. U.S. tolerance s for residues of quinoxyfen in/on the vegetable, fruiting, group 8

- 10 (1.7 ppm) ; f ruit, stone, group 12 (0.7 0 ppm) ; and hop, dried cones (3.0 ppm) are higher than the corresponding Codex MRL s for peppers (1 ppm) ; cherries (0. 4 ppm) ; and hops, dry (1 ppm)

. U.S. tolerances for residues of quinoxyfen in/on lettuce, head (7.0 ppm); lettuce, leaf (19 ppm) ; and melon, subgroup 9A ( 0 .0 8 ppm) are lower than the corresponding Codex MRL s for lettuce, head (8 ppm); lettuce, leaf (20 ppm); and melons, except watermelon (0.1 ppm)

. Canadian MRLs are established for residues of quinoxyfen per se in/on sweet cherries ; tart cherries ; hop, dried con es; and grapes (Attachment 5) . U.S. tolerances for residues of quinoxyfen in/on the fruit, stone, group 12 (0.70 ppm); hop, dried cones (3.0 ppm) ; and fruit, small, vine climbing, except fuzzy kiwifruit, subgroup 13

- 07F (2.0 ppm) are higher than the corresponding Canadian MRLs for sweet and tart cherries (0. 3 ppm) ; hop, dried co n es ( 2.5 ppm) ; and grapes ( 0 .5 ppm). Harmonization issues will be addressed during Registration Review

.

10 .0 Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, were considered in the
most recent quinoxyfen 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 c 

### .” The OPP typically considers the highest potential exposures from the lega l use of a pesticide when conducting human

- health risk assessments, including, but not limited to, people who obtain drinking water from sources near agricultural areas, the variability of diets within the U.S., and people who may be exposed when harvestin g crops. Should these

c http://www.hss.energy.gov/nuclearsafety/env/guidance/justice/eo12898.pdfQuinoxyfen Registration Review Hum an

- Health Assessment Scoping Document

________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ _____ ___ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ __

Page 11 of 23 

### highest exposures indicate potential risks of concern, OPP further refines the risk assessments to ensure that the risk estimates are based on the best available information.

11.0 Cumulative

Unlike other pesticides for which EPA ha s followed a cumulative risk approach based on a common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as to quinoxyfen and any other substances and quinoxyfen 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 quinoxyfen has a common mechanism of toxicity with other substances. For information regarding EPA’s efforts to determine which chemicals have a common mechanism o f toxicity and to evaluate the cumulative effects of such chemicals, see the policy statements released by EPA’s Office of Pesticide Programs concerning common mechanism determinations and procedures for cumulating effects from substances found to have

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

12.0 Endocrine Disruption

As required by FIFRA and the Federal Food, Drug, and Cosmetic Act (FFDCA), EPA reviews

numer ous studies to assess potential adverse outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic, and chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include endpoints which may be susceptible to endocrine influence, including effects on endocrine target organ histopathology, organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive lo ss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess growth, developmental and reproductive effects in different taxonomic groups. As part of its most recent registration decision f or potassium and sodium nitrate, EPA reviewed these data and selected the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard database. However, as required by FFDCA section 408(p), potassium and sodium nitrate are sub ject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).

EPA has developed the EDSP to determine whether certain substances (including pesticide active and other ingredients) may have an effect in humans or wildlife simil ar to an effect produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator may designate.” The EDSP employs a two

- tiered approach to making the statutorily required determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go through Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 testing is designed to identify any adverse endocrine

- related effects caused by th e substance, and establish a dose

- response relationship between the dose and the E, A, or T effect.

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/data call

- ins for the first group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. A second listQuinoxyfen Registration Review Hum an

- Health Assessment Scoping Document

________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ _____ ___ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ __

Page 12 of 23 

### of chemicals identified for EDSP screening was published on June 14, 2013 d 

### and includes some pesticides scheduled for Registration R eview and chemicals found in water

. For further information on the status of the EDSP, the policies and procedures, the lists of chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our website e



### .
In the interim, EP A is making no human health or environmental safety findings associated with the EDSP screening of quinoxyfen. Before completing this Registration Review, the Agency will make an EDSP FFDCA section 408(p) determination.

1 3 .0 Human Studies

Past quinoxyfen risk assessments rely in part on data from studies in which adult human subjects were intentionally exposed to a pesticide to determine their dermal and inhalation exposure. Many such studies, involving exposure to many different pesticides, co mprise generic pesticide exposure databases such as PHED, the ORETF Database, and the ARTF Database. EPA has reviewed all the studies supporting these multi

- pesticide generic exposure databases, and has found no clear and convincing evidence that the cond uct of any of them was either fundamentally unethical or significantly deficient relative to the ethical standards prevailing at the time the research was conducted. All applicable requirements of EPA’s Rule for the Protection of Human Subjects of Researc h (40 CFR Part 26) have been satisfied, and there is no regulatory barrier to continued reliance on these studies.

1 4 .0 Risk Assessment Updates, Data Deficiencies, and Label Revisions

The following data deficiencies were identified for quinoxyfen:

• Toxic ology:

o None.

• Residue Chemistry:

o None.

• Dietary Exposure:

o None.

• Occupational/Residential Exposure:

o None.

EPA anticipates conducting the following risk assessment updates during Registration Review:

• Toxicology:

o None.

• Residue Chemistry:

o None

.

• Dietary Exposure:

o None.

• Occupational/Residential Exposure:

o T he need for spray drift and volatilization risk assessment s for quinoxyfen will be examined during R egistration R eview

.

d See http://www.regulations.gov/#!documentDetail;D=EPA

- HQ

- OPPT

- 2009

- 0477

- 0074 for the final second list of chemicals.

e http://www.epa.gov/endo/Quinoxyfen Registration Review Hum an

- Health Assessment Scoping Document

________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ _____ ___ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ __

Page 13 of 23 

### 1 5 .0 References

Table 1

. Memoranda Relevant to Registration Review

. Author Barcode Date Title E. Evans & S. Recore D 414421 29

- AUG

- 2013 Quinoxyfen: Tier I Review of Human Incidents

J. Tyler D410694 01

- AUG

- 2013 Quinoxyfen. Occupational and Residential Exposure Assessment for Proposed Use on Fruiting Vegetable (Group 8

- 10), Small Fruit Vine Climbing Except Fuzzy Kiwifruit (Subgroup 13

- 07F), and Low Growing Berry (Subgroup 13

- 07G). G. Kramer et al

., D 410691 20

- AUG

- 2013 Quinoxyfen

. Human

- Health Risk Assessment for the Proposed Uses on Vegetable, Fruiting, Group 8

- 10; Fruit, Small Vine Climbing, Except Fuzzy Kiwifruit, Subgroup 13

- 07F; and Berry, Low Growing Subgroup 13

- 07G. G. Kramer D407728 20

- AUG

- 2013 Quinoxyfen

. Petition for the Establishment of Permanent Tolerances for Residues in/on Vegetable, Fruiting, Group 8

- 10; Fruit, Small Vine Climbing, Except Fuzzy Kiwifruit, Subgroup 13

- 07F; and Berry, Low Growing Subgroup 13

- 07G. Summary of Analytical Chemistry and R esidue Data

. G. Kramer D410693 20

- AUG

- 2013 Quinoxyfen. Chronic Aggregate Dietary (Food and Drinking Water) Exposure and Risk Assessment for Tolerances for Residues in/on Vegetable, Fruiting, Group 8

- 10; Fruit, Small Vine Climbing, Except Fuzzy Kiwifruit, Subgroup 13

- 07F; and Berry, Low Growing Subgroup 13

- 07G. D. Soderberg D392916 28

- NOV

- 2011 Quinoxyfen: Submission of Limited Field Trials on Root, Leaf Vegetable and Cereal as Rotated Crops. A. Nowotarski D375389 15

- JUN

- 2010 Quinoxyfen: Occupational Exposure/Risk Assessment for Aerial Application to Stone Fruits, Winter Squash, Gourds, Pumpkin, Artichoke, Pepper, Melons, Strawberry, and Head and Leaf Lettuce. S. Levy D374781 24

- MAR

- 2010 Quinoxyfen (055459); Registration No.: 62719

- 375. Label Amendm ent to Add Aerial Application to Registered Label. B. Hanson D351021 22

- JAN

- 2009 Quinoxyfen. Human Health Risk Assessment for the Proposed Food Use of Quinoxyfen on Stone Fruits Crop Group 12 (excluding Cherry), Artichoke, Winter Squash, (Pumpkin and Edible Gourds). W. Carr D354561 02

- DEC

- 2008 Quinoxyfen: Chronic Aggregate Dietary (Food and Drinking Water) Exposure and Risk Assessment for the Proposed Section 3 Registration on Proposed New Uses of Quinoxyfen on Stone Fruits crop group 12 (excluding ch erry), Artichoke, Winter Squash, Pumpkin and Edible Gourds (PP#8E7325). D. Wilbur D354559 06

- NOV

- 2008 Quinoxyfen. Petition for Tolerances and Uses on Winter Squash (including Pumpkin and Edible Gourd), Artichoke, and Stone Fruit (Group 12) (PP#8E7325). Summary of Analytical Chemistry and Residue Data. M. Dow D351766 21

- APR

- 2008 QUINOXYFEN

– Occupational Exposure/Risk Assessment for the Proposed Use of Quinoxyfen on Stone Fruit, Winter Squash and Artichoke G. Kramer D321331 15

- MAY

- 2006 Quinoxyfen on Peppers (Bell and Non

- Bell) (PP#3E6755), Eggplant (PP#3E6755), Melon Subgroup 9A (PP#5E6969), Strawberry (PP#5E6970), and Lettuce (Head and Leaf) (PP#5E6970). Health Effects Division (HED) Risk Assessment.Quinoxyfen Registration Review Hum an

- Health Assessment Scoping Document

________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ _____ ___ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ __

Page 14 of 23 Table 1

. Memoranda Relevant to Registration Review

. Author Barcode Date Title G. Kramer D323549 12

- MAY

- 2006 Quinoxyfen. Petitions for Tolerances and Uses on Peppers (Bell and Non

- Bell) (PP#3E6755), Eggplant (PP#3E6755), Melon Subgroup 9A (PP#5E6969), Strawberry (PP#5E6970), and Lettuce (Head and Leaf) (PP#5E6970). Summary of Analytical Chemistry and Residue Data. S. Stant on D328363 18

- APR

- 2006 Quinoxyfen: Chronic Aggregate Dietary (Food and Drinking Water) Exposure and Risk Assessment for the Proposed Section 3 Registration on Peppers (PP#3E6755); Melon Subgroup 9A (PP#5E6969); Strawberry (PP#5E6970); and Lettuce (Head and Leaf) (PP#5E6970). G. Kramer D27 7476 13

- MAY

- 2003 PP#s 1E06302 & 2E06474. Quinoxyfen On Grapes, Cherries And Hops. Health Effects Division (HED) Risk Assessment. M. Dow D285312 23

- APR

- 2003 QUINOXYFEN

- Exposure/Risk Assessment for Pesticide Handlers and Agricultural Workers from the Proposed Uses on Cherries, Grapes and Hops. G. Kramer D276835 26

- MAR

- 2003 PP#s 1E06302 & 2E06474. Quinoxyfen On Grapes, Cherries And Hops. Evaluation of Residue Data an d Analytical Methods

. G. Kramer D287938 28

- FEB

- 2003 QUINOXYFEN

- Briefing Memorandum for Meeting of Metabolism Assessment Review Committee

. G. Kramer D285314 23

- SEP

- 2002 PP#1E06302. Quinoxyfen On Grapes And Hops. Request for Petition Method Validation (PMV). G. Kramer D285353 20

- SEP

- 2002 PP#1E06302. Multiresidue Method (MRM) Testing of Quinoxyfen.



### Attachments:

Attachment 1: Quinoxyfen Identity Table. Attachment 2: Toxicology Profile for Quinoxyfen Attachment 3: Quinoxyfen Endpoint Selection Tables. Attachment 4: Summary of Registered Occupational Uses. Attachment 5: Quinoxyfen International Residue Limit Status Sheet.

cc: G. Kramer (RAB1), M. Perron (RAB1), J. Tyler (RAB1) RDI: RAB1 (8/21/13), D. Vogel (8/ 29 /13) G.F. Kramer:S10957:PY

- S:(703)305

- 5079:7509P:RAB1Quinoxyfen Registration Review Hum an

- Health Assessment Scoping Document

________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ _____ ___ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ __

Page 15 of 23 

### Attachment 1: Quinoxyfen Identity Table

.

Table A 1 .1. Quinoxyfen Nomenclature.
Chemical Structure

Common name Quinoxyfen Company name Not applicable
Chemical class Quinoline fungicide
IUPAC name 5,7

- dichloro

- 4

- quinolyl 4

- fluorophenyl ether
CAS name 5,7

- dichloro

- 4

- (4

- fluorophenoxy)quinoline
CAS # 124495

- 18

- 7
End

- use product/EP 2.08 lb ai/gal SC formulation; Quintec ® (EPA Reg. No 62719

- 375)

Table A 1 .2. Physicochemical Properties of the Technical Grade Test Compound: Quinoxyfen. 1

Parameter Value Reference Molecular weight 308.13 g/mol

Smith, Amy J., Group B: Physical and Chemical Properties of Quinoxyfen (DE

- 795) and Supplemental Properties of 3

- Hydroxy

- XDE

- 795, Dow AgroSciences, LLC, 20 December 2000. Melting point/range 106.0

- 107.5 oC pH 7.97 (1% solution in water at 22.7 °C) Density 1.097 g/cm 3 at 20 °C Vapor pressure 1.2 x 10 - 5 Pa at 20 °C Log 10 K OW (Log P) 4.66 at 20 °C

Solubility mg/L at 20 °C Distilled water 0.116 Water (pH 5) 0.128 Water (pH 7) 0.047 Water (pH 5) 0.036

n

- Hexane 9.64 Methanol 21.5 Ethyl acetate 179 Toluene 272 Acetone 116 Dichloromethane 589
Dissociation Constant K a = 2.77 x 10 - 4 , pK a = 3.56

1 Refer to D354559, 11/06/08, D. Wilbur

. N O F

Cl

ClQuinoxyfen Registration Review Hum an

- Health Assessment Scoping Document

________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ _____ ___ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ __

Page 16 of 23 

### Attachment 2: Toxicology Profile for Quinoxyfen

A2 .1 Toxicology Data Requirements

Study requirements (40 CFR §158.340) for food use of quinoxyfen are presented below. Use of the new guideline numbers does not imply that the new (1998) guideline protoco ls were used.

Study Technical Required Satisfied 870.1100 Acute Oral Toxicity

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

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

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

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

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

................................ .......................... yes yes yes yes yes yes yes yes yes yes yes yes 870.3100 90

- Day Oral Toxicity (rodent)

................................ ....... 870.3150 90

- Day Oral Toxicity (nonrodent)

................................ . 870.3200 21/28

- Day Dermal Toxicity

................................ ........... 870.3250 90

- Day Dermal Toxicity

................................ ................ 870.3465 90

- Day Inhalation Toxicity

................................ ........... yes yes yes

no

no 1 yes yes yes

--

-- 870.3700a Prenatal Developmental Toxicity (rodent)

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

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

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

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

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

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

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

................ yes yes yes yes yes yes 2

yes yes 2

yes yes 870.5100 Mutagenicity

— Bacterial Reverse Mutation Test

.......... 870.5300 Mutagenicity

— Mammalian Cell Gene Mutation Test

.. 870.5xxx Mutagenicity

— Structural Chromosomal Aberrations

... 870.5xxx Mutagenicity

— Other Genotoxic Effects

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

................. 870.6200b 90

- Day Neurotoxicity Screening Battery (rat)

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

................................ ........ yes yes

no yes yes

-- 870.7485 Metabolism and Pharmacokinetics

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

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

................................ ............................. yes

no yes no 3

-- yes 1 HED HASPOC concluded that the 28

- day inhalation study was not required at this time (K. Rury, 20

- Mar

- 2013; TXR#0056609).
2 The combined chronic toxicity/carcinogenicity study satisfies the requirement of the study.
3 Study is classified as acceptable/non

- guideline. The data reported in the study is suitable to inform risk assessment in the absence of any further data.Quinoxyfen Registration Review Hum an

- Health Assessment Scoping Document

________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ _____ ___ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ __

Page 17 of 23 

### A2 .2 T oxicity Profiles

Table A2 .2.1. Acute Toxicity Profile

- Quinoxyfen. Guideline No. Study Type MRID(s) Results Toxicity Category 870.1100 Acute oral (rat) 45360428 LD 50 >5000 mg/kg IV 870.1200 Acute dermal (rabbit) 45360501 LD 50 >2000 mg/kg III 870.1300 Acute inhalation (rat) 45360504 LC 50 >3.38 mg/L IV 870.2400 Acute eye irritation (rabbit) 45360505 Mild eye irritant III 870.2500 Acute dermal irritation (rabbit) 45360508 Not a dermal irritant IV 870.2600 Skin sensitization (guinea pig) 45360511 Buehler Method Not a dermal sensitizer ---
870.2600 Skin sensitization (guinea pig) 45360514 Magnusson

Klingman Dermal sensitizer

---

Table A2 .2. 2. Subchronic, Chronic, and Other Toxicity Profile

- Quinoxyfen.

Guideline No. Study Type MRID No . (year)/ Classification/Doses Results 870.3100 90

- Day Oral Toxicity in Rodents (rat) 45406705, 45406702 (1992) Acceptable/guideline 0, 10, 100, 250 mg/kg/day NOAEL = 10 mg/kg/day. LOAEL = 100 mg/kg/day based on decreased body weight gain in females, increased liver weights in males and slight hepatocellular hypertrophy (centrilobular and midzonal; both sexes). 870.3100 90

- Day Oral Toxicity in Rodents (mouse) 45406701 (1992) Acceptable/guideline 0, 10, 50, 100, 250 mg/kg/day NOAEL = 100 mg/kg/day. LOAEL = 500 mg/kg/day based on increased liver weights, individual cell hepatocellular necrosis and hepatocellular hypertrophy in both sexes. 870.3150 90

- Day Oral Toxicity in Non

Rodent (dog) 45406706 (1992) Acceptable/guideline when combined with
range

- finding studies 0, 10, 50, 100 mg/kg/day Range

- finding studies: 45406703 (1992) 0, 100, 500, 1000 mg/kg/day 45406704 (1993) 0, 250 mg/kg/day NOAEL = 100 mg/kg/day. LOAEL = not e stablished.

870.3200 28

- Day Dermal Toxicity (rat) 45360516 (2000) Acceptable/guideline 0, 10, 100, 1000 mg/kg/day 6 hr/day; 5 days/wk NOAEL = 1000 mg/kg/day. LOAEL = not established.

870.3700a Prenatal Developmental in Rodent (rat) 45360520 (1994) Acceptable/guideline 0, 100, 300, 1000 mg/kg/day Maternal NOAEL = 1000 mg/kg/day. LOAEL = not established. Developmental NOAEL = 1000 mg/kg/day. LOAEL = not established. 870.3700b Prenatal Developmental in Non

- Rodent (rabbit) 45360521 (1994) Acceptable/guideline 0, 20, 80, 200 mg/kg/day Range finding: 45360519 (1993) 0, 100, 300, 600, 1000 mg/kg/day Materna l NOAEL = 80 mg/kg/day. LOAEL = 200 mg/kg/day based on inanition, clinical signs, decreased body weights and body

weight gains, food consum ption

, and increased incidence of abortion. Developmenta l NOAEL = 80 mg/kg/day. LOAEL = 200 mg/kg/day based on increased incidence of abortion.Quinoxyfen Registration Review Hum an

- Health Assessment Scoping Document

________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ _____ ___ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ __

Page 18 of 23 Table A2 .2. 2. Subchronic, Chronic, and Other Toxicity Profile

- Quinoxyfen.

Guideline No. Study Type MRID No . (year)/ Classification/Doses Results 870.3800 Reproduction and Fertility Effects (rat) 45360522 (1995) Acceptable/guideline 0, 5, 20, 100 mg/kg/day Parental/Systemic NOAEL = 100 mg/kg/day. LOAEL = not established. Reproductive NOAEL = 100 mg/kg/day. LOAEL = not established. Offspring NOAEL = 20 mg/kg/day. LOAEL = 100 mg/kg/day based on decrease in first

- generation pup weights. 870.4100a Chronic Toxicity (rodent) See 870.4300. See 870.4300.

870.4100b Chronic Toxicity (dog) 45360517 Acceptable/guideline 0, 5, 20, 200 mg/kg/day NOAEL = 20 mg/kg/day. LOAEL = 200 mg/kg/day based on increased alkaline phosphatase, increased absolute and relative (to body) liver weights, and increased incidence of very slight to slight microscopic hepatic lesions.
870.4200a Carcinogenicity (rat) See 870.4300. See 870.4300.
870.4200b Carcinogenicity (mouse) 45406707 (1995) Acceptable/guideline 0, 20, 80, 250 mg/kg/day NOAEL = 80 mg/kg/day. LOAEL = 250 mg/kg/day based on decreased body weight gain in both sexes.

No evidence of carcinogenicity. 870.4300 Combined Chronic Toxicity/ Carcinogenicity (rat) 45360523 (1995) 45724201 (2001) Acceptable/guideline 0, 5, 20, 80 mg/kg/day NOAEL = 20 mg/kg/day. LOAEL = 80 mg/kg/day based on increases in severity of chronic progressive glomerulonephropathy in the males and minimal decreases in body weight and body

- weight gain in the males and females.
870.5100 Bacterial reverse mutation 45360601 (1993) Acceptable/guideline Negative for inducing reverse mutation in bacteria exposed to doses up to 5000 ug/plate (

- S9) and 1000 μg/plate (+S9). 870.5300 In vitro mammalian cell gene mutation 45360602 (1994) Acceptable/guideline Negative for inducing forward mutation in CHO (mammalian) cells treated up to 20 μg/mL (

- S9) and 80 ug/mL (+S9). 870.5375 In vitro mammalian chromosome aberration (RL) 45360604 (1994) Acceptable/guideline Negative up to 100 μg/mL (

- S9 and +S9).

870.5395 Mammalian micronucleus (mouse) 45360603 (1994) 45724203 (2001) Acceptable/guideline Negative up to 5000 mg/kg.

870.6200a Acute Neurotoxicity Screening Battery (rat) 45360515 (1999) Acceptable/guideline 0, 200, 632, 2000 mg/kg NOAEL = 2000 mg/kg. LOAEL = not established.

870.6200b Subchronic Neurotoxicity Screening Battery (rat) 45360518 (1995) Acceptable/guideline 0, 5, 20, 80 mg/kg/day NOAEL = 80 mg/kg/day. LOAEL = not established.Quinoxyfen Registration Review Hum an

- Health Assessment Scoping Document

________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ _____ ___ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ __

Page 19 of 23 Table A2 .2. 2. Subchronic, Chronic, and Other Toxicity Profile

- Quinoxyfen.

Guideline No. Study Type MRID No . (year)/ Classification/Doses Results 870.7485 Metabolism and Pharmacokinetics 45360605 (1995) 45360606 (2001) Acceptable/non

- guideline M&F: 10 or 500 mg/kg (labeled) as single oral dose or 10 mg/kg (labeled) as single oral dose followed by 10 mg/kg/day (unlabeled) orally for 14 days. M: 10 or 500 mg/kg (labeled) single oral dose or 500 mg/kg/day oral
gava ge dose for 3 days. Absorption of labeled quinoxyfen was rapid with maximum plasma concentrations occurring between 0.5 and 1.5 hours. Overall recovery of the dose ranged from 83.5

- 96.2%. Concentrations of radioactivity in the tissues were generally sli ghtly lower in males than females and in the low

- dose compared to the high

- dose group. The major metabolites identified were an acid labile conjugate of 4

- fluorophenol and 5,7

- dichloro

- 4

- hydroxyquinoline in the urine, glucuronide and/or sulfate conjugate( s) of two isomers of fluorophenyl ring

- hydroxy

- XDE

- 795 in the bile, and the parent and two isomers of fluorophenyl ring

- hydroxy

XDE

- 795 (unconjugated ) in the feces. The major route of elimination was through urine in the phenyl

- labeled quinoxyfen and through the feces in the quinoline

- labeled quinoxyfen.

Classified as non

- guideline due to several unanalyzed fractions. 870.7800 Immunotoxicity 48106301 (2010) Acceptable/guideline 0, 20, 100, 250 mg/kg/day NOAEL = 250 mg/kg/day. LOAEL = not established.Quinoxyfen Registration Review Hum an

- Health Assessment Scoping Document

________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ _____ ___ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ __

Page 20 of 23 

### Attachment 3: Quinoxyfen Endpoint Selection Tables.

Table A3.1. Summary of Toxicological Doses and Endpoints for Quinoxyfen for Use in Dietary and Non

Occupational Human

- Health Risk Assessments.

Exposure/ Scenario POD Uncertainty/ FQPA Safety Factors RfD, PAD, LOC for Risk Assessment Study and Toxicological Effects Acute Dietary (All Populations) Not applicable Not applicable Not applicable No adverse effects attributable to a single dose were observed. As a result, no hazard was identified and an endpoint was not selected to assess this exposure scenario. Chronic Dietary (All Populations) NOAEL = 20 mg/kg/day UF A = 10X

UF H = 10X

FQPA SF = 1X Chronic RfD = 0.2 mg/kg/day

cPAD = 0.2 mg/kg/day Combined chronic toxicity/carcinogenicity (rat)

LOAEL = 80 mg/kg/day based on increases in severity of chronic progressive glomerulonephropathy in the males and decreases in body weight and body

- weight gain in both sexes. Incidental Oral Short

- Term (1

- 30 days) and Intermediate

Term (1

- 6 months)

Dermal Short

Term (1

- 30 days) and Intermediate

Term (1

- 6 months)

Inhalation Short

Term (1

- 30 days) and Intermediate

term (1

- 6 months) Not applicable Not applicable Not applicable No exposure is expected because there are no residential uses. As a result, these exposure scenarios were not assessed.

Cancer (oral, dermal, inhalation) Classified as “not likely to be carcinogenic to humans” based on the absence of carcinogenicity in rats or mice.

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

- obs erved adverse

- effect level. LOAEL = lowest

- observed adverse

- effect level. UF = uncertainty factor. FQPA SF = FQPA Safety Factor. PAD = population

- adjusted dose (a = acute, c = chronic). RfD = reference dose. MOE = margin of exposure. LOC = level of concern.Quinoxyfen Registration Review Hum an

- Health Assessment Scoping Document

________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ _____ ___ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ __

Page 21 of 23 Table A 3 .2. Summary of Toxicological Doses and Endpoints for Quinoxyfen for Use in Occupational Human

- Health Risk Assessments. Exposure/ Scenario POD UFs LOC for Risk Assessment Study and Toxicological Effects Dermal Short

- Term (1

- 30 days) and Intermediate

Term (1

- 6 months) Not applicable Not applicable Not applicable A dermal endpoint was not selected. As a result, dermal exposure scenarios were not assessed.

Inhalation Short

- Term (1

- 30 days) and Intermediate

term (1

- 6 months) NOAEL = 20 mg/kg/day

Inhalation

absorption

factor =

100% UF A = 10X

UF H = 10X Occupational LOC for MOE = 100 90

- day oral toxicity (rat)

LOAEL = 100 mg/kg/day based on decreased body

- weight gain in females, increased liver weights in males and slight hepatocellular hypertrophy (centrilobular and midzonal) in both

sexes.

Two

- generation reproduction toxicity study (rat)

LOAEL = 100 mg/kg/day based on a decrease in first

- generation pup weights. Cancer (oral, dermal, inhalation) Classified as “not likely to be carcinogenic to humans” based on the absence of carcinogenicity in rats or mice
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

- ob served adverse

- effect level. LOAEL = lowest

- observed adverse

- effect level. UF = uncertainty factor. MOE = margin of exposure. LOC = level of concern.Quinoxyfen Registration Review Hum an

- Health Assessment Scoping Document

________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ _____ ___ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ __

Page 22 of 23 

### Attachment 4: Summary of Registered Occupational Uses

.
Quintec ® 

### (EPA Reg. #62719

- 375)

Crop Application equipment Applic. Rate (lb

ai/A) Max. No. Applic. per

Season Max. Seasonal Applic. Rate

(lb ai/A) PHI (days) Use Directions and Limitations

Artichokes Aerial and ground 0.13 4 0.52 none Min. RTI = 6

- 7 days Min. spray volume = 30 GPA

(ground); 5 GPA (aerial)
Cherry Ground 0.11 5 0.57 7 Min. RTI = 10

- 14 Min. spray volume = 30 GPA (ground)
Hops Ground 0.13 4 0.54 21 Min. RTI = 14 days Min. spray volume = 30 GPA (ground)

Lettuce Aerial and ground 0.098 4 0.39 1 Min. RTI = 10

- 14 days Min. spray volume = 30 GPA

(ground); 5 GPA (aerial)
Melons (Subgroup 9A) Aerial and ground 0.098 4 0.39 3 Min. RTI = 10

- 14 Min. spray volume = 30 GPA

(ground); 5 GPA (aerial) Stone fruit (Group 12) Ground 0.13 4 0.45 7 Min. RTI = 6

- 14 Min. spray volume = 30 GPA (ground)

Strawberry Aerial and ground 0.098 4 0.39 1 Min. RTI = 10

- 14 Min. spray volume = 30 GPA

(ground); 5 GPA (aerial)
Winter squash, gourds, pumpkin Aerial and ground 0.11 4 0.52 3 Min. RTI = 6

- 14 Min. spray volume = 30 GPA

(ground); 5 GPA (aerial) Fruiting Vegetables (Subgroup 8

- 10B) Aerial and ground 0.098 4 0.39 3 Min. RTI = 10

- 14 days Min. spray volume = 30 GPA

(ground); 5 GPA (aerial) Tomatoes [24(c) SLN] Ground 0.098 4 0.39 3 Min. RTI = 7

- 14 days Min. spray volume = 20 GPA (ground) Small Fruit Vine Climbing Except Fuzzy Kiwifruit (Subgroup 13

- 07F) Ground 0.11 5 0.54 14 Min. RTI =7

- 21 days Min. spray volume = 30 GPA (ground)

Low Growing Berry (Subgroup 13

- 07G) Aerial and ground 0.098 4 0.39 3 The minimum RTI is 10

- 14 days Min. spray volume = 30 GPA

(ground); 5 GPA (aerial)Quinoxyfen Registration Review Hum an

- Health Assessment Scoping Document

________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ _____ ___ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ___ ________ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ ______ __

Page 23 of 23 

### Attachment 5: Quinoxyfen International Residue Limit Status Sheet.



## International Residue Limits

Quinoxyfen (118203; Date of Request: 08/12/2013) Summary of US and International Tolerances and Maximum Residue Limits Residue Definition: US Canada Mexico 1 Codex 2
40 CFR 180.588: quinoxyfen, 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 quinoxyfen (5,7

- dichloro

- 4

- (4

- fluorophenoxy)quinoline) 5,7

- dich loro

- 4

- (4

- fluorophenoxy)quinoline quinoxyfen. The residue is fat soluble.

Commodity Tolerance (ppm) /Maximum Residue Limit (mg/kg) US Canada Mexico 1 Codex 2 Artichoke, globe 1.4 Fruit, stone, group 12 0.70 0.3 sweet cherries, tart cherries 0.4 cherries

Hop, dried cones 3.0 2.5 1 hops, dry Gourd, edible 0.20 Lettuce, head 7.0 8 Lettuce, leaf 19 20 Melon, subgroup 9A 0.08 0.1 melons, except watermelon Pumpkin 0.20 Squash, winter 0.20

Vegetable, fruiting, group 8

- 10 1.7 1 peppers 10 peppers Chili, dried Fruit, small, vine climbing, except fuzzy kiwifruit, subgroup 13

- 07F 2.0 0.5 grapes 2 grapes

Berry, low growing, subgroup 13

- 07G 1.0 1 strawberry MRLs with NO US equivalent Barley 0.01 (*) Currant, black 1 Edible offal (mammalian) 0.01 (*) Eggs 0.01 (*) Meat (from mammals other than marine mammals) 0.2 (fat)

Milk fats 0.2 Milks 0.01 Poultry, meat 0.02 (fat) Poultry, edible offal of 0.01 Sugar beet 0.03 Wheat 0.01 (*) Completed: M. Negussie; 08/16/2013
1 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.

2 * = absent at the limit of quantitation; Po = postharvest treatment, such as treatment of stored grains. PoP = processed postharvest treated commodity, such as processing of treated stored wheat. (fat) = to be measured on the fat portion of the sample. MRLs indicated as proposed have not been finalized by the CCPR and the CAC.