lsopvrazam (PC Code 129222) Dietary Exposure and Risk Assessment DP # 409592



### UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON
, D

. C

. 20460



### MEMORANDUM

DATE: July 17 , 2013 OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION



### SUBJECT: Isopyrazam. Acute, Chronic and Cancer Dietary (Food On l y) Ex posure and Risk Assessments for the Proposed To l erances with No U.S. Registration inion Imported Apple and Peanut.



### PC Code: 129222 

### DP Barcode: D409592 

### Decision Number: 465123 

### Registration Number: No t App li cab l e 

### Petition Number: 2E8039 

### Regulatory Action: Tolerance Petition 

### Assessment Type: Dietary (Food Only) 

### Case Number: Not App l icable 

### TXR Number: Not Applicable 

### CAS Number: 881685-58-1 

### MRID Number: Not Applicable 

### 40CFR § 180

. 654



### FROM: Bonnie Cropp-Koh lli gian, Environmental Scientist 

# --::::6...,.,.:.**~- ~**  

# it

Risk Assessment Branch (RAB)IV, Health Effects Division**(HE~ _**  

### THROUGH: Thurston Morton, Chemist, Senior

# Scient**st ~~**  RAB I V, HED (7509P)

Tom

# Bl:~,**Che~ ~·~-**  11 ( 1 

### f'l--11

. William Cutchin, Chemistv

# '~**=~ ~**  Dietary Expos ure Science Advisory Co uncil (DESAC) , HED (7509P)



### TO: Shaunta Hill/Driss Benmhend (RM20) Fungicide Branch, RD (7505P)



### Executive Summary
lsopyrazam i s not currently registered or proposed for use in the U.S. and there is no anticipated exposure to isopyrazam residues of concern from drinking water. Hence, acute, chronic, and

cancer dietary assessments were conducted for isopyrazam residues of concern in food only. This memorandum was reviewed by two peer re viewers of the D ESAC, per DESAC SOP 2012.1.
Acute, chronic, and cancer dietary (f ood only) exposure and risk assessments were conducted with the D iet ary Exposure Eval uation Model DEEM-FCID, Version 3.16 which uses food

Page 1 of 13Isopyrazam (PC C ode 12922 2 ) Dietary Exposure and Risk Assessment DP # 409592



### Page 2 of 13 consumption data from the U.S. Department of Agriculture’s National Health and Nutrition Examination Survey, What We Eat in America, (NHANES/WWEIA). This dietary survey was conducted from 2003 to 2008. These analyses were performed to support the proposed tolerances with no U.S. registration s f or isopyrazam in/on apple and peanut for the use s of isopyrazam in Chile and Nicaragua, respectively. All established, pending and proposed uses of isopyrazam, as of the date of this memorandum, are included in these assessments.
Conservative acute, chro nic and cancer (food only) exposure analyses were performed for the general U.S. population and various population subgroups using the same residue inputs. Maximum residues from field trials conducted at the maximum use rate s were used to estimate residues of isopyrazam (sum of syn
- (SYN534969) and anti

- (SYN534968) isomers) and the syn
- (CSCD459488 ; free and conjugated ) and anti

- (CSCD 459489 ; free and conjugated ) isomers of the tertiary alcohol metabolite (CSCD460260) . The analy ses assumed 100% crop treated and used DEEM default processing factors. In the absence of peanut processing data, the maximum theoretical processing factor for peanut oil was used.

Acute and non

- cancer chronic dietary risk estimates are not of concern fo r the general U.S. population or other population subgroups. At the 9 5 th percentile , the acute exposure results in an estimated dietary (food) risk equivalent to ≤4. 2 % of the acute population adjusted dose (a PAD ) for all populations. The estimated non

- cancer chronic dietary (food) risk is equivalent to ≤ 6.1 % of the chronic population adjusted dose ( cPAD ) for all populations

. The most highly exposed subpopulation is c hildren 1

- 2 years old f or both acute and non

- cancer chronic estimated di etary risks.

The Cancer Assessment Review Committee (CARC) classified isopyrazam as “Likely to be Carcinogenic to Humans” In the absence of mode of action data, the CARC recommended linear low dose extrapolation for cancer risk assessment. A cancer slo pe factor of 0.00629 (mg/kg/day) - 1 

### was used for the quantification of human cancer risk. The resulting estimated
cancer dietary (food) risk is 2 x 10 - 6 

### for the general U.S. population.

I. Introduction
Dietary risk assessment incorporates both exposure and toxicity of a given pesticide. For acute and non

- cancer chronic assessments, the risk is expressed as a percentage of a maximum acceptable dose (i.e., the dose that HED has concluded will result in no unreasonable adverse health effects). This dose is referred to as the population adjusted dose (PAD). The PAD is equivalent to the point of departure (POD, NOAEL, LOAEL, e.g.) divided by the required uncertainty or safety factors.

For acute and non

- can cer chronic exposures, HED is concerned when estimated dietary risk exceeds 100% of the PAD. References that discuss the acute and non

- cancer chronic risk assessments in more detail are available on the EPA/pesticides web site: “Available Information

on Assessing Exposure from Pesticides, A User’s Guide,” 21

- JUN

- 2000, web link: h ttp://www.epa.gov/fedrgstr/EPA

- PEST/2000/July/Day

- 12/6061.pdf; or see SOP 99.6 (20

- AUG

1999).Isopyrazam (PC C ode 12922 2 ) Dietary Exposure and Risk Assessment DP # 409592



### Page 3 of 13 The most recent dietary risk assessment for isopyrazam w as conducted by B. Daiss ( 8 /19/11; DP#392682 ).

II. Residue Information
Isopyrazam (SYN520453) is a broad spectrum fungicide belonging to the chemical class of ortho

- substituted phenyl amides. It is comprised of a mixture of two diasterioisomers designated syn
- (SYN534969; enantiomer) and anti

- (SYN534968; enantiomer) isomers; both of which are biologically active. Isopyrazam is not currently registered in the U.S.; however, a tolerance with no U.S. registration is currently established for residues of isopyraza m in/on banana at 0.05 ppm.

Residues of Concern
The metabolism of isopyrazam ( SYN 520453) has been studied in wheat, grape and lettuce. Previously, the HED Residues of Concern Knowledgebase Subcommittee (ROCKS) considered the residues of concern in bananas (D383286, E. Scollon, 11/22/10) and determined that the residue of concern for dietary risk assessment is the parent compound isopyrazam (sum of the sy n
isomer (SYN53496 9 ) and anti

- isomer (SYN53496 8 )) plus its monohydroxy metabolite , CSCD459488 (free and conjugated), the syn
- isomer of the tertiary alcohol metabolite (CSCD460260)

. While both the syn
- (CSCD459488) and anti

- ( CSCD 459489 ) isomers of the tertiary alcohol metabolite (CSCD460260) are judged to have similar toxicity when compared to the parent, the committee decided to include only the syn
- isomer of the tertiary alcohol metabolite (CSCD459488; free and conjugated) in the risk assessment for banana based the banana field trial data which found detectable residues of CSCD459488 (free and conjugated) in/on whole banana but not CSCD459489 (free and conjugated). However, the Committee also recommended that residues of CSCD459489 ( free and conjugated) should be analyzed for in future residue chemistry studies.
The HED isopyrazam risk assessment team has decided that it is appropriate to expand the HED ROCKS decision for banana to apple and peanut. The team has also decided to exp licitly include CSCD459489 (free and conjugated) as a residue of concern for risk assessment so that there is no ambiguity as to what residues should be analyzed for in future residue chemistry studies.
The metabolism of isopyrazam (SYN520453) has been studied in goat and hen. Based on available goat/hen metabolism and cow feeding study data, the HED isopyrazam risk assessment team has decided that the residue of concern in livestock commodities is isopyrazam (sum of syn
- (SYN534969) and anti

- (SYN534968) isomers) for tolerance enforcement and isopyrazam (sum of syn
- (SYN534969) and anti

- (SYN534968) isomers) plus its metabolites containing the CSAA798670 moiety [3

- (difluromethyl)

- 1

- methyl

- pyrazole

- 4

- methanoic acid], expressed as isopyrazam, for risk assess ment. Assuming that isopyrazam treated peanut hay is not fed to cattle in Nicaragua, HED finds that for existing and proposed uses of isopyrazam, tolerances in livestock commodities are not needed.Isopyrazam (PC C ode 12922 2 ) Dietary Exposure and Risk Assessment DP # 409592



### Page 4 of 13 Table 1. Co mpounds to be Included in the Risk Assessment and Tolerance Expression. Matrix Residues I ncluded in Dietary Risk Assessment Residues I ncluded in Tolerance Expression Plants Apple, Banana,

Peanut Isopyrazam + CSCD459488 (free and

conjugated) + CSCD459489 (free and conjugated) Isopyrazam
Rotational Crop Not applicable since there are no U.S. registrations Livestock Ruminant Isopyrazam + its metabolites convertible to the CSAA798670 moiety, expressed as isopyrazam Isopyrazam Poultry
Drinking Water Not applicable since there are no U.S. registrations Isopyrazam (SYN520453; sum of syn
- (SYN534969) and anti

- (SYN534968) isomers) = 3

- (difluoromethyl)

- 1

- methyl

- N

- [1,2,3,4

- tetrahydro

- 9

- (1

- methylethyl)

- 1,4

- methanonaphthalen

- 5

- yl]

- 1 H

- pyrazole

- 4

- carboxamide. (CAS)
CSCD459488 ( syn
- isomer of the tertiary alcohol metabolite) = 3

- (difluoromethyl)

- 1

- methyl

- N

- [(1RS, 4SR, 9RS)

- 1,2,3,4

- tetrahydro

- 9

- (2

- hydroxypropan

- 2

- yl)

- 1,4

- methanonaphthalen

- 5

- yl]pyrazole

- 4

- carboxamide(mix of two enantiomers). (IUPAC)

CSCD459489 ( anti

- isomer of the tertiary alcohol metabolite) = 3

- (difluoromethyl)

- 1

- methyl

- N

- [(1RS, 4SR, 9SR)

- 1,2,3,4

- tetr ahydro

- 9

- (2

- hydroxypropan

- 2

- yl)

- 1,4

- methanonaphthalen

- 5

- yl]pyrazole

- 4

- carboxamide(mix of two enantiomers). (IUPAC)

CSAA798670 = 3

- (difluromethyl)

- 1

- methyl

- pyrazole

- 4

- methanoic acid



### Recommended Tolerances
Isopyrazam is not currently registered for use in the U .S. A tolerance with no U.S. registration is currently established for residues of isopyrazam in/on banana at 0.05 ppm. Based on the available residue chemistry database for isopyrazam, HED is recommending tolerance s with no U.S. registration s fo r residues of isopyrazam in/on apple and peanut at 0. 7 0 ppm and 0.01 ppm, respectively. Furthermore, HED has determined that there is no reasonable expectation of finite isopyrazam residues of concern in livestock commodities from established (imported banana commodities) and proposed (imported apple and peanut commodities) uses of isopyrazam which are all non

- domestic.

Residues U sed in Acute, Chronic and Cancer Analyse s

For the acute, chronic and cancer dietary analyse s, maximum residues from field trials conducted at the maximum use rate s were used to estimate residues of isopyrazam (sum of syn
- (SYN534969) and anti

- (SYN534968) isomers) and the syn
- (CSCD459488 ; free and conjugated ) and anti

- (CSCD 459489 ; free and conjugated ) isomers of the tertiary alcohol metabolite (CSCD460260)

. The analyses assumed 100% crop treated. DEEM d efault processing factors were used for all processed commodities including dried apple (8.0), apple juice/cider (1.3), dried banana/plantain (3.9), and peanut butter (1.89). In the absence of peanut processing data, the maximum theoretical concentration factor was used for peanut oil (2.8).Isopyrazam (PC C ode 12922 2 ) Dietary Exposure and Risk Assessment DP # 409592



### Page 5 of 13 Table 2

. Residue Estimates (ppm) Used in the Isopyrazam Acute, Chronic, and Cancer Dietary Analyses

Based on Maximum Residues from Field Trials 1 Commodity Isopyrazam Tertiary Alcohol Metabolite Total Residues of Concern syn - isomer (SYN534969) anti

- isomer

(SYN534968) syn - isomer

(CSCD459488) , free and conjugated 2 anti

- isomer (CSCD 459489 ) , free and conjugated 2 Apple 3 0. 180 0.081 0.0025 0.0025 0. 266 Banana (includes plantain) 4 0.0 025 0.0025 0. 0025 0.0025 0.01 0

Peanut 0.0 025 0.0025 0.0025 0.0025 0.010 1 Residues estimates are the single sample maximums from field trials; not the highest average field trial values. Residues reported in studies at <LOQ (0.005 ppm) are estimated at 1⁄2 LOQ. 2 Given the similar molecular weights, it is not necessary to adjust the reported residues of the metabolites (CSCD459488 and CSCD459489 ; mol. wt. 375 ) to parent (sum of syn
- ( SYN5349 69 ) and anti

- (SYN534968) isomers; mol. wt. 359) equivalents. 3 Apple residue estimates are based on field trial data reflecting a 21

- day PHI. 4 Banana pulp samples (bagged or unbagged)

. 

### III. Percent Crop Treated Information

The acute, chronic and cancer analyses assumed 100% crop treated.

I V

. Drinking Water Data

Since there are no currently registered or proposed domestic uses of isopyrazam, there is no anticipated exposure to residues of concern from drinking water.

V. DEEM

- FCIDTM Program and Consumption Information
Isopyrazam acute and chronic dietary exposure assessments were conducted using the Dietary Exposure Evaluation Model software with the Food Commodity Intake Database DEEM

- FCID, Version 3.16, which incorporate s consumption data from USDA’s NHANES/WWEIA. This dietary survey was conducted from 2003 to 2008. The data are based on the reported consumption of more than 20,000 individuals over two non

- consecutive survey days. Foods “as consumed” (e.g., apple pie) are linked to EPA

- defined food commodities (e.g., apples, peeled fruit

- cooked; fresh or N/S; baked; or wheat flour

- cooked; fresh or N/S, baked) using publicly available recipe translation files developed jointly by USDA/ARS and EPA. For chronic exposu re assessment, consumption data are averaged for the entire U.S. population and within population subgroups. However, for acute exposure assessment, consumption data are retained as individual consumption events. Based on analysis of the 2003

- 2008 WWEIA consumption data, which took into account dietary patterns and survey respondents, HED concluded that it is most appropriate to report risk for the following population subgroups: the general U.S. population, all infants (<1 year old), children 1

- 2, childr en 3

- 5, children 6

- 12, youth 13

- 19, adults 20

- 49, females 13

- 49, and adults 50

- 99 years old.
For a chronic dietary exposure assessment, an estimate of the residue level in each food or food

form (e.g., orange or orange juice) on the food commodity residue list is multiplied by the average daily consumption estimate for that food/food form to produce a residue intake estimate.Isopyrazam (PC C ode 12922 2 ) Dietary Exposure and Risk Assessment DP # 409592



### Page 6 of 13 The resulting residue intake estimate for each food/food form is summed with the residue intake estimates for all other food/food f orms on the commodity residue list to arrive at the total average estimated exposure. Exposure is expressed in mg/kg body weight/day and as a percent of the cPAD. This procedure is performed for each population subgroup.
For an acute exposure assessment , individual one

- day food consumption data are used on an individual

- by

- individual basis. The reported consumption amounts of each food item can be multiplied by a residue point estimate and summed to obtain a total daily pesticide exposure for a determin istic exposure assessment, or “matched” in multiple random pairings with residue values and then summed in a probabilistic assessment. The resulting distribution of exposures is expressed as a percentage of the aPAD on both a user (i.e., only those who re ported eating relevant commodities/food forms) and a per

- capita (i.e., those who reported eating the relevant commodities as well as those who did not) basis. In accordance with HED policy, per capita exposure and risk are reported for analyses performed at all levels of refinement. However, for deterministic assessments, any significant differences in user vs. per capita exposure and risk are specifically identified and noted in the risk assessment.

V I

. Toxicological Information
HED evaluated the toxicology data base for isopyrazam and selected doses and endpoints for acute, chronic and cancer dietary risk assessments which are provided in Table 3

.
Table 3. Summary of Toxicological Doses and Endpoints for Isopyrazam for Use in Dietary Human Health

Risk Assessments
Exposure/ Scenario Point of

Departure (mg/kg/day) Uncertainty/FQPA

Safety Factors RfD, PAD, LOC for

Risk Assessment (mg/kg/day) Study and Toxicological Effects

Acute Dietary (All Populations) NOAEL= 30 UF A = 10x UF H =10x FQPA SF= 1x Acute RfD = 0.30

aPAD = 0.30 Subchronic Toxicity

– Dog LOAEL = 100 mg/kg/day based on clinical signs of toxicity (side

- to

- side head wobble) in 1 of 4 male dogs.Isopyrazam (PC C ode 12922 2 ) Dietary Exposure and Risk Assessment DP # 409592



### Page 7 of 13 Table 3. Summary of Toxicological Doses and Endpoints for Isopyrazam for Use in Dietary Human Health

Risk Assessments
Exposure/ Scenario Point of

Departure (mg/kg/day) Uncertainty/FQPA

Safety Factors RfD, PAD, LOC for

Risk Assessment (mg/kg/day) Study and Toxicological Effects

Chronic Dietary (All Populations) NOAEL= 5.5 UF A = 10x UF H =10x FQPA SF= 1x Chronic RfD = 0.055

cPAD = 0.055 Chronic Toxicity/Carcinogenicity in Rats
LOAEL = 27.6 mg/kg/day based on based on decreased body weight and body weight gain in females; increased incidences of hepatocellular hypertrophy, pigment in centrilobular hepat ocytes, eosinophilic foci of altered hepatocytes, vacuolation of centrilobular hepatocytes, bile duct hyperplasia, and bile duct fibrosis in both sexes; and brown pigment in the kidney in females.

Cancer (all routes) Classification: CARC classified isopyrazam as “Likely to be Carcinogenic to Humans”

based on increased liver and uterine endometrial epithelial tumors in female rats and increased thyroid follicular cell tumors in male rats. A cancer slope factor 0.00629 (mg/kg/day) - 1 was calculated based on an increase in liver adenomas and/or carcinomas in female rats. 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 det ermine risk associated with lower environmentally relevant human exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = 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.


### VI I

. Results/Discussion
As stated above, for acute and non

- cancer chronic assessments, HED is concerned when dietary risk exceeds 100% of the PAD. The DEEM

- FCIDTM analyses estimate the dietary exposure of the U.S. population and various population subgroups. The results reported in Table 4 a re for the general U.S. Population, all infants (<1 year old), children 1

- 2 years old , children 3

- 5 years old , children 6

- 12 years old , youth 13

- 19 years old , females 13

- 49 years old , adults 20

- 49 years old, and adults 50

- 99 years old

. Results of the Acute, Chronic and Cancer Dietary Exposure Analyses
The results of the acute, chronic and cancer (food only) dietary exposure analyses are reported in Table 4. Acute and non

- cancer chronic dietary risk estimates are not of concern for the general U.S. population or other population subgroups. At the 9 5 th percentile , the acute exposure resultsIsopyrazam (PC C ode 12922 2 ) Dietary Exposure and Risk Assessment DP # 409592



### Page 8 of 13 in an estimated dietary (food) risk equivalent to ≤4. 2 % of the acute population adjusted dose (a PAD ) for all populations. The estimated non

- cancer chronic dietar y (food) risk is equivalent to ≤ 6.1 % of the chronic population adjusted dose ( cPAD ) for all populations

. The most highly exposed subpopulation is c hildren 1

- 2 years old for both acute and non

- cancer chronic estimated dietary risks. The resulting estimate d cancer dietary (food) risk is 2 x 10 - 6 

### for the general U.S. population.

Table 4

. Summary of Dietary (Food Only) Exposure and Risk for Isopyrazam

Population Subgroup Acute Dietary 95th Percentile Chronic Dietary Cancer Dietary Exposure (mg/kg/day) % aPAD Dietary Exposure (mg/kg/day) % cPAD Dietary Exposure (mg/kg/day) Risk
General U.S. Population 0.00 1943 < 1 0.000 379 < 1 0.000 379 2 x10 - 6 All Infants (< 1 year old) 0.0 0 8291 2.8 0.00 1873 3.4

NA NA Children 1

- 2 years old 0.0 1 2554 4. 2 0.00 3379 6.1 Children 3

- 5 years old 0.00 7506 2. 5 0.00 1802 3.3 Children 6

- 12 years old 0.00 3 241 1. 1 0.000 652 1.2 Youth 13

- 19 years old 0.00 1 262 < 1 0.000 2 22 < 1 Adults 20

- 49 years old 0.000 776 < 1 0.000 1 39 < 1 Adults 50

- 99 years old 0.000 712 < 1 0.000 130 < 1 Females 13

- 49 years old 0.00 0905 < 1 0.000 156 < 1



### VII I . Characterization of Inputs/Outputs

For the acute, chronic and cancer dietary analys e s, maximum residues from field trials conducted at the maximum use rates were used to estimate residues of isopyrazam (sum of syn
- (SYN534969) and anti

- (SYN534968) isomers) and the syn
- (CSCD459488 ; free and conjugated ) and anti

- (CSCD 459489 ; free and conjugated ) isomers of the tertiary alcohol metabolite (CSCD460260) . The analyses assumed 100% crop treated and used DEEM default processing factors. In the absence of peanut processing data, the maximum theoretical processing factor for peanut oil was u sed. The Agency considers these to be highly conservative assessments. Additional refinements including the use of crop treated information and monitoring data could be incorporated into the assessment; however, since risks are not of concern, further re finement is not needed.

I X

. Conclusions
Acute, chronic and cancer dietary (food) exposure analyses were performed to support the proposed tolerances with no U.S. registrations for isopyrazam in/on apple and peanut for the use s of isopyrazam in Chile and Nicaragua, respectively. Acute and non

- cancer chronic risk estimates are not of concern

. The estimated cancer dietary (food) risk is 2 x 10 - 6 

### for the general U.S. population. HED is confident that the assessments do not underestimate risk.Isopyrazam (PC C ode 12922 2 ) Dietary Exposure and Risk Assessment DP # 409592



### Page 9 of 13 X. List of Attachments

1. Acute/Chronic/Cancer DEEM

- FCID Residue Input File. 2. Results of Acute DEEM

- FCID Dietary Exposure Analysis. 3. Results of Chronic DEEM

- FCID Dietary Exposure Analysis. 4. Results of Cancer DEEM

- FCID Dietary Exposure AnalysisIsopyrazam (PC C ode 12922 2 ) Dietary Exposure and Risk Assessment DP # 409592



### Page 10 of 13 Attachment 1 Acute and Chronic DEEM

- FCID Residue Input File

U.S. EPA Ver. 3.16, 03

- 08

- d DEEM

- FCID Acute analysis for ISOPYRAZAM Residue file name: C: \ 129222ISOPYRAZAM4

- 22

- 13.R08 Analysis Date 04

- 22

- 2013 Residue file dated: 04

- 22

- 2013/10:44:29 Reference dose (aRfD) = 0.3 mg/kg bw/day

---------------------------------------------------------------------------------- EPA Crop Def Res Adj.Factors Comme nt Code Grp Food Name (ppm) #1 #2

---------- ---- ------------------------------- ---------- ------ ------ ------- 1100007000 11 Apple, fruit with peel 0.266000 1.000 1.000 1100008000 11 Ap ple, peeled fruit 0.266000 1.000 1.000 1100008001 11 Apple, peeled fruit

- babyfood 0.266000 1.000 1.000 1100009000 11 Apple, dried 0.266000 8.000 * 1.000 1100009001 11 Apple, dried

- babyfoo d 0.266000 8.000* 1.000 1100010000 11 Apple, juice 0.266000 1.300* 1.000 1100010001 11 Apple, juice

- babyfoo d 0.266000 1.300* 1.000 1100011000 11 Apple, sauce 0.266000 1.000 1.00 0 1100011001 11 Apple, sauce

- babyfood 0.266000 1.000 1.000 9500023000 O Banana 0.010000 1.000 1.000 9500023001 O Banana

- babyfood 0.010000 1.000 1.000 9500024000 O Banana, dr ied 0.010000 3.900 * 1.000 9500024001 O Banana, dried

- babyfo od 0.010000 3.900* 1.000 9500263000 O Peanut 0.010000 1.000 1.000 9500264000 O Peanut, butter 0.010000 1.890* 1.000 9500265000 O Peanut, oil 0.010000 2.800** 1.000 9500283000 O Plantain 0.010000 1.000 1.000 9500284000 O Plantain, dried 0.010000 3.900* 1.000

* Used Deem default processing factor ** In the absence of peanut processing data, used the maximum theoretical concentration factor for peanut, oil.Isopyrazam (PC C ode 12922 2 ) Dietary Exposure and Risk Assessment DP # 409592



### Page 11 of 13 Attachment 2. Results of Acute DEEM

- FCID Dietary Exposure Anal ysis

U.S. EPA Ver. 3.16, 03

- 08

- d DEEM

- FCID ACUTE Analysis for ISOPYRAZAM NHANES 2003

- 2008 2

- Day Residue file: 129222ISOPYRAZAM4

- 22

- 13.R08 Adjustment factor #2 used. Analysis D ate: 04

- 22

- 2013/10:46:46 Residue file dated: 04

- 22

- 2013/10:44:29 RAC/FF intake summed over 24 hours Reference dose (RfD, Acute) = 0.30 mg/kg/day

=============================================================================== Summary calculations

-- per c apita:

95th Percentile 99th Percentile 99.9th Percentile Exposure % aRfD Exposure % aRfD Exposure % aRfD

---------- -------- ---------- -------- ---------- -------- Total US P opulation: 0.001943 0.65 0.006625 2.21 0.018439 6.15 All Infants: 0.008291 2.76 0.017178 5.73 0.024450 8.15 Children 1

- 2: 0.012554 4.18 0.023888 7.96 0.040909 13.64 Children 3

- 5: 0.007506 2.50 0.013218 4.41 0.022956 7.65 Children 6

- 12: 0.003241 1.08 0.006942 2.31 0.0 14494 4.83 Youth 13

- 19: 0.001262 0.42 0.003051 1.02 0.005745 1.92 Adults 20

- 49: 0.000776 0.26 0.002002 0.67 0.004814 1.60 Adults 50

- 99: 0.000712 0.24 0.001635 0.55 0.003453 1.15 Female 13

- 49: 0.000905 0.30 0.002350 0.78 0.004893 1.63Isopyrazam (PC C ode 12922 2 ) Dietary Exposure and Risk Assessment DP # 409592



### Page 12 of 13 Attachment 3

. Results of Chronic DEEM

- FCID Dietary Exposure Analysis

U.S. EPA Ver. 3.16, 03

- 08

- d DEEM

- FCID Chronic analysis for ISOPYRAZAM NHANES 2003

- 2008 2

- day Residue file name: C:129222ISOPYRAZAM4

- 22

- 13.R08 Adjustment factor #2 used. Anal ysis Date 04

- 22

- 2013/10:48:28 Residue file dated: 04

- 22

- 2013/10:44:29 Reference dose (RfD, Chronic) = .055 mg/kg bw/day

=============================================================================== Total exposure by population subgroup

------------------------------------------------------------------------------- Total Exposure

------- ---------------------------- Population mg/kg Percent of Subgroup body wt/day Rfd

-------------------------------------- ------------- ---- ------------ Total US Population 0.000379 0.7% Hispanic 0.000566 1.0% Non

- Hisp

- White 0.000324 0.6% Non

- Hisp

- Black 0.000448 0.8% Non

- Hisp

- Other 0.000455 0.8% Nursing Infants 0.001153 2.1% Non

- Nursing Infants 0.002195 4.0% Female 13+ PREG 0.000302 0.5% Children 1

- 6 0.002254 4.1% Children 7

- 12 0.000562 1.0% Male 13

- 19 0.000204 0.4% Female 13

- 19/NP 0.000237 0.4% Male 20+ 0.000132 0.2% Female 20+/NP 0.000 133 0.2% Seniors 55+ 0.000132 0.2% All Infants 0.001873 3.4% Female 13

- 50 0.000156 0.3% Children 1

- 2 0.003379 6.1% Children 3

- 5 0.001802 3.3% Children 6

- 12 0.000652 1.2% Youth 13

- 19 0.000222 0.4% Adults 20

- 49 0.000139 0.3% Adults 50

- 99 0.000130 0.2% Female 13

- 49 0.000156 0.3%

-- --------------------------------------------------------- - ------------- - -------Isopyrazam (PC C ode 12922 2 ) Dietary Exposure and Risk Assessment DP # 409592



### Page 13 of 13 Attachment 4

. Results of Cancer DEEM

- FCID Dietary Exposure Analysis

U.S. EPA Ver. 3.16, 03

- 08

- d DEEM

- FCID Chronic an alysis for ISOPYRAZAM NHANES 2003

- 2008 2

- day Residue file name: C:129222ISOPYRAZAM4

- 22

- 13.R08 Adjustment factor #2 used. Analysis Date 04

- 22

- 2013/10:49:05 Residue file dated: 04

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- 2 013/10:44:29 Q* = 0.00629

=============================================================================== Total exposure by population subgroup

------------------------------------------------------------------------------- Total Exposure

----------------------------------- Population mg/kg Lifetime risk Subgroup body wt /day (Q*= .00629)

-------------------------------------- ------------- -------------- Total US Population 0.000379 2.38E

- 06

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