UNITED STATES ENVIRONMENT AL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

DATE: 05-May-20 15 

OFFICE OF 

CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

Subject: Prohcxadione Calcium. Section 3 Registration for Use on Strawberry and 

Watercress. Chronic Dietary Exposure and Risk Assessment. 

PC Code: I 12600 DP Bar code: 0425890 

Decision No.: 489681 

Petition No.: 4E8264 

Risk Assessment T Case No.: 7030 

TXR No.: NA CAS No.: 127277-53-6 

MRID No.: None 40 CFR: § 180.547 

From: 

Through: 

To: 

William D. Wassell, Chemist l}(;!J tf'. 

Risk Assessment Branch I (RAB 1) 

Health Effects Division (HED, 7509P) 

Na

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Expos

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Dotson, 

dd, Chemist 

ure 

Ph.D.

Science 

, 

~~ 

Chemist 

Advisory 

~. 

Co

~ 

uncil 

~ 

(DESAC) 

and 

George F. Kramer, Ph.D., Branch Senior Chemist 

RAB l/II ED (7509P) 

Barbara Madden/Laura Nollen, RM 05 

Registration Division (RO; 7505P) 

Executive Summa ry 

The chronic aggregate dietary (food + drinking water) exposure and risk assessment was 

conducted using the Dietary Exposure Eva luation Model - Food Consumption Intake Database 

(DEEM-FCID, ver. 3.16), which uses food consumption data from the U.S. Department of 

Agriculture's (USDA 's) National Health and Nutrition Examination Survey, What We Eat in 

America (NHANES/WWEIA). This dietary survey was conducted from 2003 to 2008. The 

current assessment is being conducted in support of a proposed use of prohexadione calcium on 

strawberry and watercress. This memorandum was reviewed by two peer reviewers of the 

DESAC, per DESAC SOP 20 12.1. 

The unrefined chronic analysis assumed DEEM (ver. 7.81) default processi ng factors, 100% crop 

treated (CT), and tolerance-level residues for all commodities. The chronic analysis also 

incorporated the drinking water estimates provided by Environmental Fate and Effects Division 

(EFED). The estimated drinking water concentrations (EDWCs) were generated using the rice 

mode l and are considered highly conservative. The assessment is based on the maximum 

appli cation rate of 0. 1375 lb ai/Napplication for watercress, applied using ground equipment 

Page I of7 
Prohexadione Calcium Dietary Exposure and Risk Assessment DP#425890 

with a second application 7 days after the initial application. An EDWC of 0.17 ppm was used 

in the chronic analysis. The resulting chronic food plus drinking water exposure estimates are 

not of concern to HED (<100% chronic population-adjusted dose (cPAD) for all population 

subgroups of interest). The resulting chronic exposure estimate for children 1-2 years (the 

subgroup with the greatest risk) was 19% of the cPAD. 

There is no study with a single dose and endpoint appropriate for the acute scenario and there is 

no evidence of carcinogenic potential. Therefore, these risk assessments were not performed. 

I. Introduction 

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

and chronic assessments, the risk is expressed as a percentage of a maximum acceptable dose 

(i.e., the dose which HED has concluded will result in no unreasonable adverse health effects). 

This dose is referred to as the PAD. The PAD is equivalent to a point-of-departure (POD; e.g., 

no-observable-adverse-effect-level (NOAEL)) divided by the required uncertainty or safety 

factors. 

For acute and non-cancer chronic exposures, HED is concerned when estimated dietary risk 

exceeds l 00% of the PAD. References which discuss the acute and chronic risk assessments in 

more detail arc available on the EP Npesticides web site: "Available Information on Assessing 

Exposure from Pesticides, A User's Guide," 612 1100, web link: 

http://www.epa.gov/fedrgstr/EPA-PEST/2000/July/Day-l 2/606 l .pdf; or see SOP 99.6 (8/20/99). 

The most recent prohexadione calcium dietary exposure assessment was conducted by G. 

Kramer (5/ 17/ 11 , D384707). 

II. Residue Information 

Residues of Concern: The HED Metabolism Assessment Review Committee (MARC) 

concluded that only the parent compound needs to be included in the tolerance expression for 

pome fruit and peanuts and that it is the only compound to be included in the dietary and 

drinking water risk assessments (DP# 263502, 417100, G. Kran1er). This conclusion has been 

extended to strawberry and watercress. 

Established/Recommended Tolerances: Prohexadione calcium tolerances are established in 40 

CFR §180.547. Tolerances for residues in/on all commodities are expressed in terms of the 

parent only. Based on the results of the strawberry and watercress field trials, the appropriate 

tolerance levels for residues of prohexadione calcium inion strawberry is 0.30 ppm and inion 

watercress is 4.0 ppm (Memo, pending, W. Wassell, D41998 l). 

Residues Used in the Chronic Analysis: This analysis employed tolerance-level residues for all 

commodities. The DEEM (ver. 7.81) default processing factor of 1.3 for apple juice was set to 1.0 

because prohexadione calcium does not concentrate in this commodity (Memo, 11 /22/99, G. 

Kramer, D252547). 

Page 2 of7 
Prohexadione Calcium Dietary Exposure and Risk Assessment DP#425890 

Fish: The USDA Pesticide Data Program (PDP) monitored pesticide residues in catfish in 2008, 

2009, and 2010. In general, pesticide residues would not be expected to be found in fish unless 

the pesticide bioaccumulates or has an aquatic use. To determine whether or not residues are 

present in fish, HED now routine ly checks PDP monitoring data regardless of the pesticide's 

uses and physicochemical properties. However, PDP did not analyze catfish samples for 

prohexadione calcium. As a result, residues in fish were not included in the assessment. 

III. Estimated Drinking Water Concentrations 

Drinking water residues were incorporated directly into the chronic dietary analysis ("water, 

direct, all sources" and "water, indirect, all sources") and were provided by EFED (Memo, 

0 1/30/20 15, E. Seifu, et al., D419983). The EDWCs were generated using the watercress 

application scenario and the Tier 1 Rice Model for prohexadione calcium. The assessment is 

based on the maximum application rate of0.1375 lb ai/A/application for watercress, applied 

using ground equipment with a second application 7 days after the initial application. 

Table I. Tier I EDWCs Resulting From Grou nd Applications of Prohexadione Calcium. 

Drinking water source Use Acute EDWC Chronic EDWC 30-year average 

(model) (modeled rate) (ppb) (ppb) (ppb) 

Surface water (Tier I Watercress 170 170 NR1 

Rice Model) (0.275 lb ai/Nyear) 

Groundwater Turf 0. 137 0. 137 NR 

(SCI GROW) (19.5 lbs ai/A/year) 

1 NR = not reported. 

An EDWC of 0.17 ppm was used in the chronic analysis. 

IV. DEEM-FCID Progr am and Consumption Information 

A prohexadione calcium chronic dietary exposure and risk assessment was conducted using 

DEEM-FCID (ver. 3. 16), which uses food consumption data from the USDA's 

NHANES/WWEJA. This dietary survey was conducted from 2003 to 2008. Foods "as 

consumed" (e.g., apple pie) are li nked 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 rec ipe translation files developed jointly by USDA/ARS and EPA. For chronic 

exposure assessment, consumption data are averaged for the entire U.S. population and within 

population subgroups. Based on analysis of the 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 (< I year old), 

children 1-2, children 3-5, children 6-12, youth 13- 19, adults 20-49, females 13-49, and adults 

50-99 years old. 

For chronic dietary exposure assessment, an estimate of the residue level in each food or foodform (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. 

The resulting residue intake estimate for each food/food form is summed with the residue intake 

estimates for all other food/food forms on the commodity residue list to arrive at the total 

Page 3 of7 
Prohexadione Calcium Dietary Exposure and Risk Assessment DP#425890 

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. 

V. Toxicological Information 

The toxicological endpoints are summarized below in Table 2. 

Table 2. Summary of Toxicological Doses and Endpoints for Prohexadione Calcium fo r Use in Dietary Human 

Health Risk Assessments'. 

Exposure Dose Used in Risk RfD, PAD, LOC for Risk 

Scenario Assessment, UFs Assessment Study and Toxicological Effects 

Acute Dietary NA NA There is no study with a single dose and 

endpoint appropriate for this scenario. 

Therefore, this risk assessment was not 

performed. 

Chronic Dietary NOAEL = 20 Chronic RID = cPAD = Chronic toxicity - dog. 

mg/kg/day 0.20 mg/kg/day 

LOA EL = 200 mg/kg/day based on 

UFA= IOX hisropathological changes in the kidneys 

UF11 = IOX (dilated basophilic tubules) and increased 

FQPASF = IX urinary volume and Na• ion 

concentrations. 

Cancer (oral, Not likely human NA No evidence of carcinogenic potential, 

dermal, inhalation) carcinogen. therefore, cancer risk assessment is not 

required. 1 UF = uncertainty factor, FQPA SF = FQPA safety factor, NOAEL = no-observed adverse-effect level, 

LOAEL = lowest-observed adverse-effect level, UFA = extrapolation from animal to human 

(interspecies), UF11 = potential variation in sensitivity among members of the human population 

(intraspecies), PAD = population-adjusted dose (c = chronic), Rm = reference dose, LOC = level of 

concern. 

VI. Results/Discussion 

An unrefined chronic analysis was performed using DEEM-FCID (ver. 3. 16) which estimates the 

dietary exposure of the U.S. population and various population subgroups. The results reported 

are for the general U.S. population, all infants (< I 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. 

The resulting chronic risk estimates are not of concern to HED. The most highly exposed 

population was children 1-2 years old utilizing 19% of the cPAO. See Table 3 below for a 

summary of the results of the dietary assessment. 

Page 4 of7 
Prohexadione Calcium Dietary Exposure and Risk Assessment DPf/425890 

Table 3. Summary of Dietary (Food and Drin king Water) Expos ure Risk fo r Prohexadione Calcium.' 

Acute Dietary 

(951

h Percentile) 

Population Subgroup Dietary 

Exposure %aPAD 

(mg/kg/day) 

General U.S. Population 

All Infants (<I year old) 

Children 1-2 years old 

Children 3-5 years old 

Children 6-12 years old NIA NIA 

Youth 13- 19 years old 

Adults 20-49 years old 

Adults 50-99 years old 

Females 13-49 years old 1 The values for the highest exposed population arc bolded. 

NA = not applicable. 

VII. Characterization of Inputs/Outputs 

Chronic Dietary Cancer 

Dietary Dietary 

Exposure %cPAD Exposure Risk 

(mg/kg/day) (mg/kg/day) 

0.007637 3.8 

0.029740 15 

0.038201 19 

0.022459 II 

0.010120 5.1 NIA NIA 

0.005035 2.5 

0.005172 2.6 

0.005198 2.6 

0.005329 2.7 

The chronic analysis assumed tolerance-level residues, DEEM (ver. 7.81 ) default processing 

factors, and I 00% CT. This analysis is considered very conservative and could be refined 

through the use of anticipated-residue estimates (ARs) for all commodities, %CT data for 

registered commodities, and/or additional empirical processing factors. 

VIII. Conclusions 

A chronic exposure and risk assessment was conducted using DEEM-FCID (ver. 3. 16), which 

incorporates food consumption data from the USDA's NHANES/WWEIA. This dietary survey 

was conducted from 2003 to 2008. 

The unrefined chronic analysis assumed DEEM (ver. 7.8 1) default processing factors, 100% CT, 

and tolerance-level residues for all commodities. The chronic analysis also incorporated the 

drinking water estimates provided by EFED. The resulting chronic food plus water exposure 

estimates are not of concern to HED (< I 00% chronic cPAD) for all population subgroups of 

interest, and the resulting chronic exposure estimate for children 1-2 years (the subgroup with the 

greatest risk) was 19% of the cPAD. 

IX. List of Attachments 

Attachment 1: DEEM-FCID Chronic Residue File. 

Attachment 2: DEEM-FCID Chronic Exposure and Risk Estimates. 

cc: W.Wassell (RABI ) 

ROI: DE SAC Reviewers: 5/2/20 1 1 

Page 5 of7 
Prohexadione Calcium Dietary Exposure and Risk Assessment 

Attachment 1: DEEM-FCID Chronic Residue File. 

Filename : J : \Work Files\$ Prohexadione\DEEM\PROHEXADIONE.R08 

Chemical: Prohexadione 

RfD(Chronic) : . 2 mg/kg bw/day NOEL(Chronic): O mg/kg bw/day 

RfD(Acute): O mg/kg bw/day NOEL{Acute): O mg/kg bw/day 

DP#425890 

Date created/last modified: 01 - 07-2015/16 : 54:50 Program ver. 3.16, 03-08-d 

EPA Crop 

Code Grp Commodity Name 

Def Res 

(ppm) 

1100007000 11 

1100008000 11 

1100008001 11 

1100009000 11 

1100009001 11 

1100010000 11 

1100010001 11 

1100011000 11 

1100011001 11 

1100129000 11 

1100210000 11 

1100266000 11 

1100266001 11 

1100267000 11 

1100268000 11 

1100268001 11 

1100310000 11 

1201090000 12A 

1201090001 12A 

1201091000 12A 

1201091001 12A 

1307359000 13G 

1307359001 13G 

1307360000 13G 

1307360001 13G 

3100046 001 31 

3100048000 31 

3100049000 31 

3100049001 31 

3200170000 32 

3200172000 32 

3200173000 32 

3400292000 34 

3400292001 34 

3400294000 34 

3400295000 34 

3500340000 35 

3500342000 35 

3500343000 35 

8601000000 86A 

8602000000 86B 

9500263000 0 

9500264000 0 

9500265000 0 

9500398000 0 

Apple, fruit with peel 

Apple, peeled fruit 

Apple, peeled fruit- babyfood 

App le , dried 

Apple, dried- babyfood 

Apple, juice 

Apple, juice-babyfood 

Apple , sauce 

Apple, sauce-babyfood 

Crabapple 

Loquat 

Pear 

Pear- baby food 

Pear, dried 

Pear, juice 

Pear, juice -babyfood 

Quince 

Cherry 

Cherry-babyfood 

Cherry, juice 

Cherry, juice-babyfood 

Strawberry 

Strawberry-babyfood 

Strawberry, juice 

Strawberry, juice-babyfood 

Beef, meat byproducts-babyfood 

Beef, kidney 

Beef, liver 

Beef, liver-babyfood 

Goat, meat byproducts 

Goat, kidney 

Goat, liver 

Pork, meat byproducts 

Pork, meat byproducts-babyfood 

Pork, kidney 

Pork, liver 

Sheep, meat byproducts 

Sheep, kidney 

Sheep, liver 

Water, direct, all s ources 

Water, indirect, a ll s ources 

Peanut 

Peanut , butter 

Peanut, oil 

Watercress 

Page 6 of7 

Adj . Factors 

Ill 112 

3.000000 

3.000000 

3.000000 

3.000000 

3.000000 

3.000000 

3.000000 

3.000000 

3.000000 

3.000000 

3.000000 

3.000000 

3.000000 

3.000000 

3.000000 

3.000000 

3.000000 

0.400000 

0 . 400000 

0.400000 

0 .400000 

0.300000 

0.300000 

0.300000 

0.300000 

0.050000 

0.100000 

0.050000 

0.050000 

0.050000 

0 . 100000 

0.050000 

0.050000 

0.050000 

0.100000 

0 . 050000 

0.050000 

0 . 100000 

0.050000 

0.170000 

0.170000 

1.000000 

1.000000 

1.000000 

4 . 000000 

1.000 

1.000 

1.000 

8.000 

8.000 

1 . 000 

1.000 

1 . 000 

1. 000 

1 . 000 

1. 000 

1.000 

1. 000 

6.250 

1.000 

1.000 

1 . 000 

1 . 000 

1.000 

1 . 500 

1. 500 

1.000 

1. 000 

1.000 

1.000 

1.000 

1 . 000 

1.000 

1 .000 

1 . 000 

1.000 

1.000 

1.000 

1.000 

1.000 

1.000 

1 . 000 

1.000 

1 . 000 

1 . 000 

1 . 000 

1.000 

1.890 

1.000 

1. 000 

Comment 

1 . 000 

1.000 

1 .000 

1 . 000 

1. 000 

1.000 

1. 000 

1.000 

1. 000 

1.000 

1. 000 

1.000 

1 . 000 

1.000 

1 .000 

1.000 

1. 000 

1.000 

1. 000 

1.000 

1. 000 

1 . 000 

1 . 000 

1 . 000 

1 . 000 

1.000 

1.000 

1.000 

1. 000 

1.000 

1. 000 

1.000 

1. 000 

1 . 000 

1 . 000 

1. 000 

1 . 000 

1.000 

1. 000 

1. 000 

1.000 

1. 000 

1. 000 

1.000 

1. 000 
Prohexadione Calcium Dietary Exposure and Risk Assessment DP#425890 

Attachment 2: DEEM-FCID Chronic Exposure and Risk Estimates. 

US EPA 

DEEM-FCID Chronic analysis 

Residue file name: J: \Work 

Ver . 3 . 16 , 03-08-d 

for PROHEXADIONE NHANES 2003-2008 2-day 

Files\$ Prohexadione\DEEM\PROHEXADIONE.R08 

Adjustment factor ff2 NOT used . 

Analysis Date 01-07 - 2015/16:56:47 Residue file dated : 01 - 07 - 2015/16:54:50 

Reference dose (RfD, Chronic) = . 2 mg/ kg bw/day 

============================================ ======== === === =================== 

Population 

Subgroup 

Total US Population 

Hispanic 

Non-Hisp-White 

Non-Hisp- Black 

Non-Hisp-Other 

Nursing Inf ants 

Non-Nursing Infants 

Female 13+ PREG 

Children 1-6 

Children 7 - 12 

Male 13-19 

Female 13-19/NP 

Male 20+ 

Female 20+/NP 

seniors 55+ 

All Infants 

Female 13-50 

Children 1-2 

Children 3-5 

Children 6-12 

Youth 13-19 

Adults 20-49 

Adults 50-99 

Female 13-49 

Total exposure by population subgroup 

To tal Exposure 

mg/kg 

body wt/day 

0.007637 

0 . 009236 

0.007249 

0.007429 

0.009151 

0.016200 

0 . 035788 

0 . 006493 

0.027070 

0.008968 

0.004745 

0 . 005287 

0 . 004921 

0.005382 

0.005163 

0.029740 

0.005340 

0 . 038201 

0 . 022459 

0.010120 

0.005035 

0 . 005172 

0 . 005198 

0 . 00 53 29 

Page 7 of7 

Percent of 

Rf d 

3.8% 

4.6% 

3.6% 

3. 7% 

4 .6% 

8.1% 

17.9% 

3.2% 

13.5% 

4 . 5% 

2. 4% 

2.6% 

2.5% 

2.7% 

2 . 6% 

14.9% 

2 . 7% 

19 .1% 

11. 2% 

5 .1% 

2 . 5% 

2.6% 

2 . 6% 

2. 7%