
                 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
                            WASHINGTON, D.C.  20460
                                       
                                       
              OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION



MEMORANDUM			

Date:  March 21, 2013		

SUBJECT:	Naphthalene Acetates- Chronic Dietary and Drinking Water Exposure and Risk Assessment for Section 3 New Use of Naphthalene Acetic Acid-ester on Avocado, Mango, Mamey Sapote, Rambuttan, and the Expansion to Pome Fruit Crop Subgroup 11-10.
.  

PC Code:  056003 (NAA potassium salt)
DP Barcode: D404399
Decision No.:  461439
Registration No.: 87320-E
Petition No.:  2F7991
Regulatory Action:  Section 3
Risk Assessment Type:  Dietary
Case No.:  0379
TXR No.:  NA
CAS No.:  2122-70-5
MRID No.:  NA
40 CFR:  §180.155 (a) & (b)

FROM:	Thurston G. Morton, Chemist
            Risk Assessment Branch IV
            Health Effects Division (7509P)

THROUGH:	Dennis McNeilly, Chemist
		Meheret Negussie, Chemist
		Dietary Exposure Science Advisory Council (DESAC)
            Health Effects Division (7509P)
            
TO:		Tony Kish, Chemical Review Manager
		Fungicide Branch
      Registration Division (7505P)
		


This document provides chronic dietary (food and drinking water) risk analyses of exposures resulting from use of naphthalene acetates as plant activators on food crops.  Executive Summary

Chronic dietary risk assessment was conducted for naphthalene acetates 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 Examination Survey, What We Eat in America, (NHANES/WWEIA).  This dietary survey was conducted from 2003 to 2008.    The analysis was performed to support a Section 3 request for use of naphthalene acetates (NAA) on avocado, mango, and mamey sapote and the expansion of the Crop Subgroup 11-10.
   
Acute Dietary Exposure Results and Characterization

There were no toxicological effects attributable to a single exposure (dose) of NAA 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 100 percent crop treated assumptions were used.  DEEM default processing factors were used to modify the tolerance values.  The chronic analysis incorporated the 10 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 0.003 mg/kg/day or 2% of the cPAD.   The chronic dietary exposure estimate for the general population is 0.0005 mg/kg/day or <1% of the cPAD.   

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, LOAEL, e.g.) divided by the required uncertainty or safety factors.

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/July/Day-12/6061.pdf ; or see SOP 99.6 (20-AUG-1999).

The most recent dietary risk assessment for NAA was conducted by B. Daiss (DP 397389, 1/31/12).
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 avocado, mango, and mamey sapote and the expansion of the Crop Subgroup 11-10.  Residues used in the acute and chronic dietary analyses are provided in Table 1.

Table 1. Tolerance Values Used in Naphthalene Acetates Dietary Exposure Analyses
RAC
Tolerance (ppm)
Pome 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
Proposed New Use
Recommended Tolerance
Avocado
0.05
Mango
0.05
Mamey Sapote
0.05
Rambuttan
2.0
 
 III.	Drinking Water Data

The Tier I Estimated Drinking Water Concentrations (EDWCs) for use in the human health risk assessment for 1-naphthaleneacetic acid were calculated using FIRST (surface water) and SCIGROW (ground water) drinking water models (D293886, J.L. Melendez, 9/25/03).  These values generally represent upper-bound estimates of the concentrations of 1-naphthaleneacetic acid equivalents that might be found in surface and ground water due to the use of 1-naphthalenacetic acid on olives, which represents the highest use rate scenario.  Both models provide estimates suitable for screening purposes.  Modeled EDWCs are presented in Table 2.




Table 2. Tier I Estimated Drinking Water Concentrations of 1-Naphthaleneacetic acid[1]
Chemical
Acute (peak) Surface Water Concentration (ppb)
Annual Average Surface Water Concentration (ppb)
Ground Water Concentration (ppb)
NAA
22.3
2.99
0.0226

IV.	DEEM-FCID(TM) Program and Consumption Information

Naphthalene acetates chronic dietary exposure assessment was 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 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 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 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 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, 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 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.  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 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

 HED evaluated the toxicology data base for naphthalene acetates and selected the following doses and endpoints for acute and chronic dietary and drinking water risk assessments.  









Table 3. Summary of Toxicological Doses and Endpoints for Naphthalene acetates for Use in Dietary and Non-Occupational Human Health Risk Assessments
Exposure Scenario
                              Point of Departure
                       Uncertainty/ FQPA Safety Factors
                       RfD, PAD, LOC for Risk Assessment
                        Study and Toxicological Effects
                                       
                                       
Acute Dietary (General Population)
An acute RfD for the general population or any population subgroups was not selected because no effect attributable to a single (or few) day(s) oral exposure was observed in animal studies.
Chronic Dietary 
(All Populations)
NOAEL = 15 mg/kg/day
UFA= 10x
UFH=10x
FQPA SF= 1x
Chronic RfD = 0.15
mg/kg/day
cPAD = 0.15 mg/kg/day
Chronic Toxicity - Dog  
LOAEL = 75  mg/kg/day based on emesis, corpuscular regurgitation incidences, gross and histopathological changes in stomachs and sinusiodal histiocytosis in livers in males
Cancer (all routes)
Not a Human Carcinogen
Point of Departure (POD) = A data point or an estimated point that is derived from observed dose-response data and  used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures.  NOAEL = no observed adverse effect level.  
NOAEL = no observed adverse effect level.  
LOAEL = lowest observed adverse effect level.  
UF = uncertainty factor.  
UFA = extrapolation from animal to human (interspecies).  
UFH = potential variation in sensitivity among members of the human population (intraspecies).  
FQPA SF = FQPA Safety Factor.  
PAD = population adjusted dose (a = acute, c = chronic).  
RfD = reference dose.  

VI.	Results/Discussion

As stated above, for chronic assessments, HED is concerned when dietary risk exceeds 100% of the PAD.  The DEEM-FCID(TM) 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 (<1 year old), children 1-2, children 3-5, children 6-12, youth 13-19, females 13-49, adults 20-49, and adults 50-99 years.













Results of Chronic Dietary Exposure Analysis

Table 4.  Summary of Chronic Dietary Exposure and Risk for NAA
                              Population Subgroup
                               cPAD (mg/kg/day)
                                    Chronic
                                       
                                       
                             Exposure (mg/kg/day)
                                    % cPAD
General U.S. Population
                                     0.15
                                   0.000513
                                     <1
All Infants (< 1 year old)
                                       
                                   0.001487
                                      1.0
Children 1-2 years old
                                       
                                   0.002945
                                      2.0
Children 3-5 years old
                                       
                                   0.001868
                                      1.2
Children 6-12 years old
                                       
                                   0.000774
                                     <1
Youth 13-19 years old
                                       
                                   0.000383
                                     <1
Adults 20-49 years old
                                       
                                   0.000305
                                     <1
Adults 50-99 years old
                                       
                                   0.000303
                                     <1
Females 13-49 years old
                                       
                                   0.000317
                                     <1


VI.	Characterization of Inputs/Outputs

The chronic dietary analysis is conservative.  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.  

VII.	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, children 1-2 years of age, is 0.003 mg/kg/day or 2% of the cPAD.  

VIII.	List of Attachments

1.  Chronic DEEM-FCID Residue Input File.
2.  Results of Chronic DEEM-FCID Dietary Exposure Analysis.
Attachment 1 Chronic DEEM-FCID Residue Input File

Filename: C:\Documents and Settings\tmorton\My Documents\MyFiles\DEEM Files\056003 NAA\2E7991\056003 Chronic 2F7991.R08
Chemical: NAA
RfD(Chronic): .15 mg/kg bw/day  NOEL(Chronic): 0 mg/kg bw/day
RfD(Acute): 0 mg/kg bw/day  NOEL(Acute):  0 mg/kg bw/day
Date created/last modified: 10-24-2012/10:08:49       Program ver. 3.16, 03-08-d
-----------------------------------------------------------------------------------
   EPA     Crop                                   Def Res     Adj.Factors   Comment
   Code     Grp  Commodity Name                    (ppm)       #1    #2   
---------- ---- -------------------------------  ----------  ------ ------  -------
0103296000 1C   Potato, chips                      0.010000   1.000  1.000  
0103297000 1C   Potato, dry (granules/ flakes)     0.010000   6.500  1.000  
0103297001 1C   Potato, dry (granules/ flakes)-b   0.010000   6.500  1.000  
0103298000 1C   Potato, flour                      0.010000   1.000  1.000  
0103298001 1C   Potato, flour-babyfood             0.010000   1.000  1.000  
0103299000 1C   Potato, tuber, w/peel              0.010000   1.000  1.000  
0103299001 1C   Potato, tuber, w/peel-babyfood     0.010000   1.000  1.000  
0103300000 1C   Potato, tuber, w/o peel            0.010000   1.000  1.000  
0103300001 1C   Potato, tuber, w/o peel-babyfood   0.010000   1.000  1.000  
1001240000 10A  Orange                             0.100000   1.000  1.000  
1001241000 10A  Orange, juice                      0.100000   1.800  1.000  
1001241001 10A  Orange, juice-babyfood             0.100000   1.800  1.000  
1001242000 10A  Orange, peel                       0.100000   1.000  1.000  
1001369000 10A  Tangerine                          0.100000   1.000  1.000  
1001370000 10A  Tangerine, juice                   0.100000   2.300  1.000  
1100007000 11   Apple, fruit with peel             0.150000   1.000  1.000  
1100008000 11   Apple, peeled fruit                0.150000   1.000  1.000  
1100008001 11   Apple, peeled fruit-babyfood       0.150000   1.000  1.000  
1100009000 11   Apple, dried                       0.150000   8.000  1.000  
1100009001 11   Apple, dried-babyfood              0.150000   8.000  1.000  
1100010000 11   Apple, juice                       0.150000   1.300  1.000  
1100010001 11   Apple, juice-babyfood              0.150000   1.300  1.000  
1100011000 11   Apple, sauce                       0.150000   1.000  1.000  
1100011001 11   Apple, sauce-babyfood              0.150000   1.000  1.000  
1100129000 11   Crabapple                          0.150000   1.000  1.000  
1100173500 11   Goji berry                         0.150000   1.000  1.000  
1100210000 11   Loquat                             0.150000   1.000  1.000  
1100266000 11   Pear                               0.150000   1.000  1.000  
1100266001 11   Pear-babyfood                      0.150000   1.000  1.000  
1100267000 11   Pear, dried                        0.150000   6.250  1.000  
1100268000 11   Pear, juice                        0.150000   1.000  1.000  
1100268001 11   Pear, juice-babyfood               0.150000   1.000  1.000  
1100310000 11   Quince                             0.150000   1.000  1.000  
1201090000 12A  Cherry                             0.100000   1.000  1.000  
1201090001 12A  Cherry-babyfood                    0.100000   1.000  1.000  
1201091000 12A  Cherry, juice                      0.100000   1.500  1.000  
1201091001 12A  Cherry, juice-babyfood             0.100000   1.500  1.000  
8601000000 86A  Water, direct, all sources         0.003000   1.000  1.000  
8602000000 86B  Water, indirect, all sources       0.003000   1.000  1.000  
9500020000 O    Avocado                            0.050000   1.000  1.000  
9500215000 O    Mango                              0.050000   1.000  1.000  
9500215001 O    Mango-babyfood                     0.050000   1.000  1.000  
9500216000 O    Mango, dried                       0.050000   1.000  1.000  
9500217000 O    Mango, juice                       0.050000   1.000  1.000  
9500217001 O    Mango, juice-babyfood              0.050000   1.000  1.000  
9500235000 O    Olive                              0.700000   1.000  1.000  
9500236000 O    Olive, oil                         0.700000   1.000  1.000  
9500279000 O    Pineapple                          0.050000   1.000  1.000  
9500279001 O    Pineapple-babyfood                 0.050000   1.000  1.000  
9500280000 O    Pineapple, dried                   0.050000   5.000  1.000  
9500281000 O    Pineapple, juice                   0.050000   1.700  1.000  
9500281001 O    Pineapple, juice-babyfood          0.050000   1.700  1.000  
9500333000 O    Sapote, Mamey                      0.050000   1.000  1.000  
Attachment 2  Results of Chronic DEEM-FCID Dietary Exposure Analysis

U.S. EPA                                                        Ver. 3.16, 03-08-d
DEEM-FCID Chronic analysis for NAA                         NHANES 2003-2008 2-day
Residue file name: C:\Documents and Settings\tmorton\My Documents\MyFiles\DEEM Files\056003 NAA\2E7991\056003 Chronic 2F7991.R08
                                                 Adjustment factor #2 NOT used.
Analysis Date 10-24-2012/10:24:55     Residue file dated: 10-24-2012/10:12:06
Reference dose (RfD, Chronic) = .15 mg/kg bw/day
===============================================================================
                    Total exposure by population subgroup
-------------------------------------------------------------------------------

                                                    Total Exposure
                                         -----------------------------------
          Population                         mg/kg             Percent of   
           Subgroup                       body wt/day             Rfd       
--------------------------------------   -------------       ----------------
Total US Population                         0.000513                 0.3%
Hispanic                                    0.000735                 0.5%
Non-Hisp-White                              0.000448                 0.3%
Non-Hisp-Black                              0.000597                 0.4%
Non-Hisp-Other                              0.000600                 0.4%
Nursing Infants                             0.000880                 0.6%
Non-Nursing Infants                         0.001757                 1.2%
Female 13+ PREG                             0.000544                 0.4%
Children 1-6                                0.002154                 1.4%
Children 7-12                               0.000682                 0.5%
Male 13-19                                  0.000396                 0.3%
Female 13-19/NP                             0.000369                 0.2%
Male 20+                                    0.000299                 0.2%
Female 20+/NP                               0.000302                 0.2%
Seniors 55+                                 0.000304                 0.2%
All Infants                                 0.001487                 1.0%
Female 13-50                                0.000320                 0.2%
Children 1-2                                0.002945                 2.0%
Children 3-5                                0.001868                 1.2%
Children 6-12                               0.000774                 0.5%
Youth 13-19                                 0.000383                 0.3%
Adults 20-49                                0.000305                 0.2%
Adults 50-99                                0.000303                 0.2%
Female 13-49                                0.000317                 0.2%

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