aphthalene acetates Dietary Exposure and Risk Assessment DP #: 426996 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHI NGTON, D.C. 20460 

OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION 

MEMORANDUM 

Date: November 18, 20 15 

SUBJ ECT: Naphthalene Acetates- Chronic Dietary and Drinking Water Exposure and Risk 

Assessment for Section 3 New Use of Naphthalene Acetic Acid-ester on 

Pomegranate. 

PC Code: 05600 I, 056002. 056003, 056004. 056007, 

056008 

Decision No.: 495111 

Petition No.: 4E83 I 0 

Risk Assessment Type: Dietary 

TXR No.: NA 

MRID No.: NA 

FROM: 

THROUGH: Elissa Reaves, Ph.D., Chief 

Risk Assessment Branch 4 

Health Effects Division (7509P) 

DP Barcode: 0 426996 

Registration No.: 87320-E 

Regulatory Action: Section 3 

Ca se No.: 0379 

C AS No.: 2 122-70-5 

40 CFR: § 180.155 (a) & (b) 

~~ 

and 1 1 I 

/i y I y rt . William Cutchin, Chemist f;-~.:..I"' l -G· fv:-. 

Kristin Rury, Biologist g/:/ / . ~ Dietary Exposure Science AdvisbrY ~I {12)ESAC) 

HED (7509P) 

TO: Sidney Jackson/Barbara Madden 

Minor Use & Emergency Response Branch 

Registration Division (7505P) 

This document provides chronic dietary (food and drinking water) risk ana lyses of exposures 

resulting from use of naphthalene acetates as plant activators for the new use on pomegranate. 

Page I of IO 
~hthalene acetates Dietary Exposure and Risk Assessment DP #: 426996 

Executive Summary 

Chronic dietary risk assessment was conducted for naphthalene acetates using the Dietary 

Exposure Evaluation Model software with the Food Commodity Intake Database (DEEMFCID), Version 3. 16, which incorporates 2003-2008 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). The analysis was performed to support a 

Section 3 request for use of naphthalene acetates (NAA) on pomegranate. 

This memorandum was reviewed by two peer reviewers of the DESAC, per DESAC SOP 

20 12.1. 

Acute Dietary Exposure Results and Characterization 

There were no toxicological effects attributable to a single exposme (dose) ofNAA observed in 

oral toxicity studies including the developmental toxicity studies in rats or rabbits. Therefore, a 

dose and an endpoint for acute dietary exposure were not identified for NAA and a quantitative 

acute dietary exposure assessment was not conducted. 

Chronic Dietary Exposure Results and Characterization 

A conservative chronic dietary and drinking water exposure analysis was performed for the 

general U.S. population and various population subgroups. Tolerance level residues and I 00 

percent crop treated assumptions were used. DEEM default processing factors were used to 

modify the tolerance values. The chronic analysis incorporated the I 0 year average surface 

drinking water estimate from application of naphthalene acetates to olives. The chronic dietary 

exposure estimate for the highest exposed population subgroup, children 1-2 years of age, is 

0.036203 mg/kg/day or 15% of the cPAD. The chronic dietary exposure estimate for the 

general population is 0.013977 mg/kg/day or 5.6% of the cPAD. 

Cancer Dietary Exposure Results and Characterization 

Naphthalene acetates is considered "not likely to be a human carcinogen;" therefore, 

quantification of human cancer risk is not required. 

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 point of departure (POD, 

NOAEL, lowest observed adverse effect level (LOAEL), e.g.) divided by the required 

uncertainty or safety factors. 

Page 2of 10 
Naphthalene acetates Dietary Exposure and Risk Assessment DP #: 426996 

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

exceeds 100% of the PAD. References which discuss the acute and 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: 

http://www.epa.gov/fedrgstr/EPA-PEST/2000/J uly/Day-1 2/6061.pdf; or see SOP 99.6 (20-

AUG-1999). 

The most recent dietary risk assessment for NAA was conducted by T. Morton (DP 404399, 

3/2 1/ 13). 

II. Residue Information 

1-Naphthaleneacetic acid (NAA), its salts, ester, and acetamide are plant growth regulators 

which are collectively referred to as naphthalene acetates. They are currently registered for use 

on various orchard and fruit crops including apple, cherry, olive. orange, pear, tangelo, and 

tangerine. Naphthalene acetates are used to prevent preharvest drop of fruits, thin fruit trees, and 

delay flower induction. Tolerances for residues of naphthalene acetates in/on food and feed 

commodities are currently established under 40 CFR § 180.155, and are expressed in terms of 1-

naphthaleneacetic acid, [ethyl ester of 1-naphthaleneacetic acid, and naphthaleneacetamide]. 

The petitioner has requested Section 3 for use of naphthalene acetates on pomegranate. Residues 

used in the chronic dietary analyses are provided in Table 1. 

Table I. Tolera nce Values Used in Naphtha lene Acetates Dietary Exposure A nalyses 

RAC Tolerance (ppm) 

Pomc Fruit Subgroup 11-10 0. 15 

Cherry. sweet 0. 1 

Olive 0.7 

Oranges 0.1 

Pineapple 0.05 

Tangerine 0.1 

Avocado 0.05 

Potato Seed Piece 0.01 

Mango 0.05 

Marney Sapote 0.05 

Rambutan 2.0 

Proposed New Use Recommended Tolerance 

Pomegranate 0.05 

The USDA Pesticide Data Program (PDP) monitored pesticide residues in catfish in 2008, 2009, 

and 20 l 0. PDP did not ana lyze catfish samples for NAA residues. As a result, residues in fish 

were not included in the assessment. 

Page 3of 10 
Naphthalene acetates Dietary Exposure and Risk Assessment DP #: 426996 

III. Percent Crop Treated Information 

The chronic dietary exposure assessment assumed that 100% of the proposed and registered 

crops were treated with naphthalene acetates ( 100% CT). 

IV. Drinking Water Data 

Tier I Estimated Drinking Water Concentrations (EDWCs) in surface and groundwater for 1-

naphthaleneacetic acid (NAA) and its associated salts 1-naphthaleneacetic acid, sodium salt 

(NAA sodium salt) and 1-naphthaleneacetic acid, potassium salt (NAA potassium salt), ethyl 

ester (NAA ethyl ester) and acetamide (NAA acetamide) 1 were provide for use in the dietary 

exposure assessment. The EDWCs were calculated using the Tier 1 surface water aquatic model 

FIRST and the Tier l/Il groundwater model PRZM-GW (in Tier I mode). The Environmental 

Fate and Effects Division (EFED) has reviewed a proposed Interregional Research 4 (IR-4) and 

registrant petition to register the use of NAA ethyl ester for the use on pomegranate for 

controlling basal trunk sprouts and root suckers (J. Melendez, 0423410, 5/4/ 15). The maximum 

single application rate is 3.6 lb a.e./A2, with two applications allowed at 60 day intervals, for the 

product Tre-Hold® Sprout Inhibitor A- 112 (EPA Reg. No. 5481-429, containing I lb a.e./gallon). 

Only ground applications are allowed on pomegranate, diluted in a large volume of water, 

applied to the lower tree trunks and immediate surrounding area. Previously, the maximum rate 

allowed was for the use on olives (single application at 0.33 lb a.e./A). Since this new use 

represents a higher application rate than previously calculated, and no groundwater values 

derived from PRZM-GW were previously calculated, new EDWCs are hereby calculated and 

provided. 

Table 2. Maximum T ier I Estimated Drinking Water Concentra tions (EDWCs) for drinking water 

assessment for a ll NAA related compounds (collectively known as n a phthalene acetates), based on 

1roun d a pp r . 1cahon o f N AA 6 . . I ethyl ester on pomee:ranates a t 3. lb a.e./A x 2 a pphcattons•vear 

DRINKING WATER MAX ~lllM ESTll\IATED DRINKING 

SOURCE (MODEL USED) SCENARIO (rate modeled per crop cycle) WATER CONCENTRATIOI" (EDWC) 

Cnnb) 

Groundwater (PRZM- WI sand/7.2 lb a.e./A/yr Acute 789 

GW) WI sand/7.2 lb a.e./A/yr Chronic 646 

Surface water (FIRST) Index Reservoir/7.2 lb a.e./A/yr Acute 440 

Index Reservoir/7 .2 lb a.e./ A/yr Chronic 65.1 

V. DEEM-FCID Program and Consumption Information 

Naphthalene acetates 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 incorporates consumption data from USDA's National Health and Nutrition 

I Collectively known as naphthalene acetates. 

2 The abbreviation a.e. refers to acid equivalents (i. e., the lbs ofNAA ethyl ester, expressed as lbs ofNAA acid). 

Page 4of10 
Naphthalene acetates Dietary Exposure and Risk Assessment DP #: 426996 

Examination Survey, What We Eat in America, (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 NIS; 

baked; or wheal flour - cooked; fresh or N/S, baked) using publicly available recipe translation 

files developed jointly by USDNARS and EPA. For chronic exposure assessment, consumption 

data are averaged for the entire U.S. population and within population subgroups, but for acute 

exposure assessment are retained as individual consumption events. Based on ana lysis 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 (< I year old), children 1-2, 

children 3-5, children 6-1 2, 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. The resulting residue consumption 

estimate for each food/food form is summed with the residue consumption estimates for all other 

food/food forms 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. 

VI. Toxicological Information 

HED evaluated the toxicology data base for naphthalene acetates and selected the following 

doses and endpoints for dietary risk assessments. 

Page 5 of JO 
Naphthalene acetates Dietary Exposure and Risk Assessment DP #: 426996 

Table 4.5.4.1. Summary of Toxicological Endpoints for Naphthalene Acetates for Use in Dietary a nd NonOccupational Huma n Health rusk Assessments 

Point of Uncertainty/FQP RID, PAD, Study and Toxicological Effects' 

Exposure/Scenario LOC for Risk Depa rture A Safety Factors Assessment 

Acute Dietary An acute RID for the general population or any population subgroups was not selected because no (General 

Population) 

effect attributable to a single day oral exposure was observed in animal studies. 

Co-critical Dog Studies with NAA Na salt: 

Subchronic Toxicity (MRID 4298380 I) 

Chronic Toxicity (MR1D 43744201) 

Chronic RID = Subchronic LOAEL = 150 mg/kg/day based 

Subchronic UF"= IOx 0.25 on GI tract lesions and hypocellularity of the 

Chronic Dietary NOA EL= UF11= IOx mg/kg/day bone marrow 

(All Populations) 25 FQPASF= Ix Subchronic NOAEL= 25 mg/kg/day 

mg/kg/day cPAD = 0.25 

mg/kg/day Chronic LOA EL= 75 mg/kg/day based on 

stomach lesions in 75% of the males and 

slight sinusoidal histiocytosis in the liver of 

50% of the males 

Chron ic NOAEL = 15 mg/kg/day 

Cancer Bioassay in rats and mice not carcinogenic. Not mutagenic. 

VII. Results/Discussion 

As stated above, for chronic assessments, HED is concerned when dietary risk exceeds I 00% of 

the PAD. The DEEM-FCID analyses estimate the dietary exposure of the U.S. population and 

various population subgroups. The results reported in Table 4 are for the general U.S. 

Population, all infants (< I year old), children 1-2, children 3-5, children 6- 12, youth 13-19, 

fema les 13-49, adults 20-49, and adults 50-99 years. 

Results of Chronic Dietary Exposure Analysis 

T a ble 4. Summarv of C hronic Dictarv Exoosure a nd Risk for NAA 

Population Subgroup cPAD (mg/kg/day) 

C hronic 

Exposure (me/kg/day) %cPAD 

General U.S. Pooulation 0.0 13977 5.6 

All Infants(< I year old) 0.036203 15 

Children 1-2 years old 0.022367 8.9 

Children 3-5 years old 0.018232 7.3 

Children 6-12 years old 0.25 0.012575 5.0 

Youth 13-19 years old 0.010202 4.1 

Adu lts 20-49 years old 0.013738 5.5 

Adults 50-99 years old 0.013583 5.4 

Females 13-49 years old 0.01370 1 5.5 

Page 6of 10 
Naphthalene acetates Dietary Exposure and Risk Assessment DP #: 426996 

VIII. Characterization of Inputs/Outputs 

The chronic dietary analysis is conservati ve. Tolerance level residues used in the analysis are 

expected to exceed the residues actually consumed. In addition, the 100% crop treated estimate 

used for all crops in the assessment will considerably overestimate the actual percent crop 

treated. 

IX. Conclusions 

Based on screening level analyses of estimated dietary risks for the general U.S. population and 

various population subgroups, the chronic dietary exposure estimates for naphthalene acetates 

are significantly below HED's level of concern for all supported commodities. The chronic 

dietary exposure estimate for the highest exposed population subgroup, all infants < l year old, is 

0.036203 mg/kg/day or 15% of the cPAD. 

X. List of Attachments 

1. Chronic DEEM-FCID Residue Input File. 

2. Results of Chronjc DEEM-FCID Dietary Exposure Analysis. 

Page 7 of IO 
Naphthalene acetates Dietary Exposure and Risk Assessment DP #: 426996 

Attachment I Chronic DEEM-FCID Residue Input File 

Filename: C:\Users\tmorton\Documents\My Files\DEEM Files\056003 NAA\4E8310 Pomegranate\056003 

Chronic4E8310 Food and Water.ROS 

Chemical: NAA 

RfD(Chronic): . 25 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 

Date created/last modified : 05-22-2015/07:08:27 Program ver. 3.16, 03-08-d 

----------------------------------------------------------------------------------- EPA Crop 

Code Grp Commodity Name 

Def Res 

(ppm) 

0103296000 lC 

01032 97000 lC 

0103297001 lC 

0103298000 lC 

0103298001 lC 

0103299000 lC 

0103299001 lC 

0103300000 lC 

0103300001 lC 

1001240000 lOA 

1001241000 lOA 

1001241001 lOA 

1001242000 lOA 

1001369000 lOA 

1001370000 lOA 

1100007000 11 

1100008000 11 

1100008001 11 

1100009000 11 

1100009001 11 

110001 0000 11 

1100010001 11 

1100011000 11 

1100011001 11 

1100129000 11 

1100210000 11 

1100266000 11 

1100266001 11 

1100267000 11 

1100268000 11 

1100268001 11 

110031 0000 11 

1201090000 12A 

1201090001 12A 

1201091000 12A 

1201091001 12A 

8601000000 86A 

8602000000 86B 

9500020000 0 

9500215000 0 

9500215001 0 

9500216000 0 

9500217000 0 

9500217001 0 

9500235000 0 

9500236000 0 

9500279000 0 

9500279001 0 

9500280000 0 

9500281000 0 

9500281001 0 

9500289000 0 

9500333000 0 

Potato, chips 

Potato, dry (granules/ flakes) 

Potato, dry (granules/ flakes)-b 

Potato, flour 

Potato, flour-babyfood 

Potato, tuber, w/peel 

Potato, tuber, w/peel-babyfood 

Potato, tuber, w/o peel 

Potato, tuber, w/o peel-babyfood 

Orange 

Orange, juice 

Orange, juice-babyfood 

Orange, peel 

Tangerine 

Tangerine, juice 

Apple, fruit with peel 

Apple, peeled fruit 

Apple, peeled fruit-babyfood 

Apple, dried 

Apple, dried-babyfood 

Apple, juice 

Apple, juice-babyfood 

Apple, sauce 

Apple, sauce-babyfood 

Crabapple 

Loquat 

Pear 

Pear-babyfood 

Pear, dried 

Pear. juice 

Pear, juice-babyfood 

Quince 

Cherry 

Cherry-baby food 

Cherry, juice 

Cherry, juice-babyfood 

Water, direct, all sources 

Water, indirect, all sources 

Avocado 

Mango 

Mango-babyfood 

Mango, dried 

Mango, juice 

Mango , juice-babyfood 

Olive 

Olive, oil 

Pineapple 

Pineapple-babyfood 

Pineapple, dried 

Pineapple, juice 

Pineapple, juice-babyfood 

Pomegranate 

Sapote, Marney 

0.010000 

0.010000 

0.010000 

0.010000 

0.010000 

0 . 010000 

0 . 010000 

0.010000 

0 . 010000 

0.100000 

0.100000 

0.100000 

0.100000 

0 .100000 

0.100000 

0.150000 

0.150000 

0.150000 

0 .150000 

0.150000 

0.150000 

0.150000 

0.150000 

0.150000 

0.150000 

0.150000 

0.150000 

0.150000 

0.150000 

0.150000 

0.150000 

0.150000 

0.100000 

0.100000 

0.100000 

0.100000 

0.646000 

0.646000 

0.050000 

0.050000 

0.050000 

0.050000 

0.050000 

0.050000 

0.700000 

0.700000 

0.050000 

0.050000 

0 . 050000 

0.050000 

0.050000 

0.050000 

0.050000 

Page 8of10 

Adj.Factors 

Ill 112 

1. 000 1. 000 

6 .500 1.000 

6.500 1.000 

1. 000 1. 000 

1. 000 1. 000 

1. 000 l. 000 

1. 000 1. 000 

1.000 1. 000 

1. 000 1. 000 

1. 000 1. 000 

1. BOO 1. 000 

l. 800 l. 000 

l. 000 1. 000 

1. 000 l. 000 

2. 300 1. 000 

1.000 1.000 

1. 000 1. 000 

l. 000 1. 000 

8.000 l.000 

8. 000 1. 000 

l.300 1.000 

1.300 1.000 

l. 000 1. 000 

1. 000 l. 000 

1.000 1. 000 

1. 000 1. 000 

l .000 1.000 

1. 000 l. 000 

6.250 1.000 

1.000 l. 000 

l. 000 1. 000 

1. 000 1. 000 

l. 000 l. 000 

1. 000 l. 000 

1. 500 1. 000 

1. 500 1. 000 

1.000 l.000 

l. 000 l. 000 

l. 000 l. 000 

l.000 l.000 

1 . 000 1.000 

l. 000 1. 000 

1. 000 1. 000 

1. 000 1. 000 

l.000 l.000 

1.000 1.000 

1.000 1.000 

l. 000 l. 000 

5. 000 1. 000 

l. 700 1. 000 

l. 700 1. 000 

1.000 1.000 

l. 000 l. 000 

Comment 
Naphthalene acetates Dietary Exposure and Risk Assessment 

Attachment 2 Results of Chronic DEEM-FCID Dietary Exposure Analysis 

FOOD and Water 

DP #: 426996 

us EPA Ver. 3.16. 03-08-d 

DEEM-FCID Chronic analysis for NAA NHANES 2003-2008 2-day 

Residue file name: C:\Users\tmorton\Documents\My Files\DEEM Files\OS6003 NAA\ 4E8310 

Pomegranate\05600 3 Chronic4E8310 Food and Water . ROS 

Adjustment factor U2 used. 

Analysis Date 09-ll-2015/12:44:S7 Residue file dated: 09 -11- 2015/12:43 :13 

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

Total exposure by population subgroup 

Total Exposure 

Popula tion 

Subgroup 

Total US Population 

Hispanic 

Non- Hisp-White 

Non-Hisp-Black 

Non-Hisp-Other 

Nursing Infants 

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 SS+ 

All Infants 

Female 13 -so 

Children 1-2 

Children 3-S 

Children 6-12 

Youth 13-19 

Adults 20-49 

Adults S0-99 

Female 13-49 

mg/kg 

body wt/ day 

0. 013977 

0. 013S90 

0. 014296 

0.011706 

0. 016118 

0 .013061 

0.046S39 

0. 013221 

0.019399 

0. 011907 

0 . 0096Sl 

0 .010741 

0 .012842 

0.014443 

0 .013322 

0 .036203 

0. 013719 

0 .022367 

0 .018232 

0 .012S75 

0.010202 

0 .013738 

0.013S83 

0.013701 

Page 9 of 10 

Percent of 

Rfd 

S.6\ 

S.H 

S.7\ 

4. 7\ 

6.4\ 

S.2\ 

18 .6\ 

s .3\ 

7.8\ 

4.8\ 

3.9\ 

4 .3\ 

S .l\ 

S.8\ 

S.3\ 

14 . S\ 

5.5\ 

8.9\ 

7. 3\ 

5.0\ 

4 .1\ 

S.S\ 

s .4\ 

S.5\ 
Naphthalene acetates Dietary Exposure and Risk Assessment DP #: 426996 

Food Only 

US EPA Ver. 3.16, 03 -0 8-d 

DEEM - FCID Chronic analysis for NAA NHANES 2003-2008 2 - day 

Residue file name: C:\Users\tmorton\Documents\My Files\DEEM Files\056003 NAA\4E8 310 

Pomegranate\056003 Chronic4E8310 Food Only.ROS 

Adjustment factor #2 used. 

Analysis Date 09 -11 -201 5/12 :45:24 Residue file dated: 09-11-2015/12:43 : 52 

Reference dose (RfD, Chronic) = .25 mg/ kg bw/ day 

============================================================a================== 

To tal exposure by population subgroup 

Population 

Subgroup 

Total US Population 

Hispanic 

Non-Hisp-White 

Non- Hisp-Black 

Non- Hisp-Other 

Nursing Infants 

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 

mg/kg 

body wt/day 

0.000450 

0 .000675 

0 .000383 

0 .000545 

0 .000528 

0 .000823 

0.001548 

0.000484 

0 .002074 

0.000630 

0 .000352 

0 . 000321 

0.000240 

0 .000236 

0.000244 

0.001325 

0 .000257 

0 .002854 

0.001792 

0 .00071 9 

0 .000338 

0.000242 

0 .000241 

0.000255 

Page 10of10 

Percent of 

Rf d 

0.2\ 

0 .3\ 

0.2\ 

0.2\ 

0.2\ 

o. 3\ 

0.6\ 

0.2\ 

0.8\ 

0. 3\ 

0 . 1\ 

0 . 1\ 

0 .1\ 

0 .1\ 

o.n 

0.5\ 

0 . 1\ 

1.1\ 

0.7\ 

0 .3\ 

0.1\ 

0 .1\ 

0 . 1\ 

0.1\