Document ID: EPA-HQ-OPP-2009-0141-0007
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2010-04-07T04:00Z

SEQ CHAPTER \h \r 1 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

                                         WASHINGTON, D.C.  20460

                                                                        
                                                                    
OFFICE OF              

PREVENTION, PESTICIDES

                                                                        
                                                                      
AND TOXIC SUBSTANCES 

MEMORANDUM

Date:  	10/22/2009

SUBJECT:  Aminopyralid Chronic Aggregate Dietary (Food and Drinking
Water) Exposure and Risk Assessment for the Section 3 Registration on
Field Corn

    

 

PC Code:  005100 	DP Number:  D369212

Decision No: 401475 	Registration No:  62719-519 

Petition Nos.:  8F7455	Regulatory Action:  Section 3 Registration 

Risk Assess Type:  None	Case No.:  None 

TXR No.:  None	CAS No.:  566191-89-7

MRID No.:   None 	40 CFR:  180.610

      	

FROM:  	Douglas Dotson, Ph.D., Chemist

	Risk Assessment Branch II

Health Effects Division (7509P)  SEQ CHAPTER \h \r 1 		

		

THROUGH:	Donna Davis, Chemist

		William Cutchin, Chemist

	Dietary Exposure Science Advisory Council

Health Effects Division (7509P)

		

TO:	Kathryn Montague/Joanne Miller, RM Team 23

Herbicide Branch

Registration Division (7505P)

	

Executive Summary

DEEM-FCID™, Version 2.03, which uses food consumption data from the
U.S. Department of Agriculture’s Continuing Surveys of Food Intakes by
Individuals (CSFII).  The surveys were taken from 1994-1996 and included
a supplemental children’s survey taken in 1998.  The analysis was
performed to support a Section 3 tolerance petition for the use of
aminopyralid on field corn.  An acute dietary assessment was not
performed, as a toxicological endpoint attributable to a single dose has
not been identified for aminopyralid.  Aminopyralid is classified as
“not likely to be carcinogenic to humans;” therefore, a cancer
assessment was not performed.

The unrefined chronic assessment is based on the assumption that
aminopyralid residues are present at tolerance levels in all commodities
for which tolerances have been established, and that 100% of those crops
are treated.  DEEM™ Version 7.81 default processing factors were
applied to all processed commodities for which they were available. 
Drinking water was incorporated directly into the dietary assessment
using the estimated drinking water concentration (EDWC) for surface
water generated by the Tier 1 FQPA Index Reservoir Screening Tool
(FIRST) Model.

The resulting chronic dietary exposure estimates for food and water
combined are well below HED’s level of concern for the general U.S.
population and all population subgroups.  Using the DEEM-FCID software,
dietary exposure is estimated at 0.000703 mg/kg/day for the U.S.
population (<1% of the chronic population adjusted dose (cPAD)) and
0.002097 mg/kg/day (<1% of the cPAD) for children 1 to 2 years old, the
population subgroup with the highest estimated chronic dietary exposure
to aminopyralid.  

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 population adjusted dose
(PAD).  The PAD is equivalent to the point of departure (PoD; e.g.
NOAEL, LOAEL, etc.) 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 website:  “Available Information on
Assessing Exposure from Pesticides, A User’s Guide,” 21-JUN-2000,
web link:      HYPERLINK
"http://www.epa.gov/fedrgstr/EPA-PEST/2000/July/Day-12/6061.pdf" 
http://www.epa.gov/fedrgstr/EPA-PEST/2000/July/Day-12/6061.pdf  ; or see
SOP 99.6 (20-AUG-1999).

II.	Residue Information

Residues of Concern:  The nature of the residue of aminopyralid in
plants and livestock has been adequately delineated based on metabolism
studies conducted with aminopyralid in wheat, grass, lactating goats,
and laying hens.  In metabolism studies reflecting foliar applications
to grass and wheat, aminopyralid was found to be metabolized to a
multi-component mixture of water-soluble complexes that consist mostly
of isomeric mixtures of acid- and base-labile N-glucosides and glucose
ester conjugates of aminopyralid.  HED concluded that the residues of
concern in grass and small grain commodities are free and conjugated
aminopyralid.  Metabolism studies in lactating goats and laying hens
show that most of the administered dose is rapidly excreted (~80% for
hens and ~95% for goat).  The weight of the evidence is that the limited
amount of aminopyralid that is not excreted remains as the parent
compound.  Therefore, the residue of concern in livestock is
aminopyralid (Memo, D360100, D. Dotson, 10/22/2009).

Tolerances:  Permanent tolerances have been established under 40 CFR
§180.610(a) for free and conjugated residues of aminopyralid in or on
grass and wheat commodities at levels ranging from 0.04 ppm in wheat
grain to 50 ppm in grass hay.  Permanent tolerances have also been
established residues of aminopyralid in or on the following animal
commodities:  milk (0.03ppm), kidney of cattle, goat, horse, and sheep
(0.3 ppm), and the fat, meat, and meat byproducts (except kidney) of
cattle, goat, horse, and sheep (0.02 ppm).

Dow AgroSciences has proposed tolerances for residues of aminopyralid on
field corn grain, forage, and stover.  HED has reviewed residue data
submitted to support these uses and concluded that the proposed
tolerances are appropriate (Memo, D. Dotson, D360100, 10/22/2009).  The
tolerances are listed in Table 1, below.  Field corn grain is the only
human food item on this list.

Table 1.  Aminopyralid Recommended Tolerances

Crop Commodity	Recommended Tolerance (ppm)

Field Corn Grain	0.20

Field Corn Forage	0.30

Field Corn Stover	0.20

Livestock:  Livestock feedstuffs associated with the proposed uses
include field corn grain, forage, silage, stover, and milled byproducts.
 Tolerances are currently in effect for animal commodities.  Based on
recalculated dietary burdens and the results of ruminant and poultry
feeding studies, HED concluded that no changes need to be made to the
animal commodity tolerances.

EEM™ Version 7.81 default processing factors were applied to all
processed commodities for which they were available.  The only processed
commodities in this assessment are corn syrup and dried beef. 
Processing studies for these two commodities were not submitted by the
registrant.  

 Drinking Water Data

The drinking water residues used in the dietary risk assessment were
provided by the Environmental Fate and Effects Division (EFED, Memo, R.
Barris, D361926, 7/24/2009).  Water residues were incorporated directly
into the DEEM-FCID assessment under the food categories “water,
direct, all sources” and “water, indirect, all sources.”   

The residue of concern in drinking water is parent aminopyralid (Memo,
D301689, M. Doherty, 7/12/2005).  EFED estimated residues of
aminopyralid in surface water and groundwater using the FIRST and
SCIGROW (Screening Concentrations in Groundwater) models, respectively. 
The models and their descriptions are available at the EPA internet
site:   HYPERLINK "http://www.epa.gov/oppefed1/models/water/" 
http://www.epa.gov/oppefed1/models/water/ .  The maximum estimated
drinking water concentrations (EDWCs) are presented below in Table 2.

Table 2.  Maximum Aminopyralid EDWCs in Surface and Ground Water

Maximum Surface Water EDWC (ppb)	

Maximum Ground Water Acute/Chronic EDWC (ppb)

Acute Value	

Chronic/Cancer Value

	

10.024

	

1.937	

0.630

The chronic surface water EDWC was higher than the groundwater EDWC;
therefore, the surface water value of 1.937 ppb was used in the chronic
dietary assessment.  The acute surface water value is not relevant to
this dietary assessment, as a toxic effect attributable to a single dose
has not been identified for aminopyralid.

™ Program and Consumption Information

An aminopyralid chronic dietary exposure assessment was conducted using
the Dietary Exposure Evaluation Model software with the Food Commodity
Intake Database DEEM-FCID™, Version 2.03, which incorporates
consumption data from USDA’s Continuing Surveys of Food Intakes by
Individuals (CSFII), 1994-1996 and 1998.  The 1994-96, 98 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 1994-96, 98
CSFII 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+
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

Reference:   Aminopyralid.  Human Health Risk Assessment for the
Proposed Use on Field Corn (PP#8F7455), D359088, D. Dotson, et al.,
10/22/2009.

HED has evaluated the available toxicity data for aminopyralid and
determined that the following endpoints and doses are appropriate for
use in the dietary risk assessment:

Table 3. Summary of Toxicological Doses and Endpoints for Aminopyralid
for Use in

Dietary Human Health Risk Assessments

Exposure/

Scenario	Point of Departure	Uncertainty/

FQPA Safety Factors	RfD, PAD, Level of Concern for Risk Assessment	Study
and Toxicological Effects

Acute Dietary (General Population, including Infants and Children and
females 13-49)	N/A	

N/A

	N/A	

A toxic effect attributable to a single exposure was not seen in the
toxicity database; therefore, an acute endpoint has not been identified.

Chronic Dietary (All Populations)

 	NOAEL= 50 mg/kg/day

	UFA= 10 x

UFH=10 x

FQPA SF=1x

	Chronic RfD = RfD=0.5 mg/kg/day 

cPAD 0.5 mg/kg/day	Chronic toxicity/carcinogenicity study

LOAEL=500mg/kg/day

based on cecal enlargement, slight mucosal hyperplasia in males and
slightly decreased body weights

Cancer (oral, dermal, inhalation)	Classification:  “Not likely to be
Carcinogenic to Humans” based on the absence of significant tumor
increases in two adequate rodent carcinogenicity studies.

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. 
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.  N/A =
not applicable.

 

The FQPA Safety Factor has been reduced to 1x for all population
subgroups for the following reasons:  1)  there is no evidence of
increased pre- and/or post-natal sensitivity/susceptibility to
aminopyralid, 2) there is no evidence of neurotoxicity in the database
(so a developmental neurotoxicity (DNT) study has not been required),
and 3) the exposure values that are used in the risk assessment are
conservative and are unlikely to underestimate risk.

VI.	Results/Discussion 

M-FCID™ analyses estimate the dietary exposure of the U.S. population
and various population subgroups.  The results reported in Table 3 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+ years.  

Aminopyralid chronic dietary (food + water) exposure estimates using the
DEEM-FCID™ software are well below HED’s level of concern for the
U.S. population and each of the population subgroups.  Dietary exposure
was estimated to be 0.000703 mg/kg/day for the U.S. population (<1% of
the cPAD) and 0.002097 mg/kg/day (<1% of the cPAD) for the most highly
exposed population subgroup (children, 1-2 years old).  The estimated
exposures and risks from residues of aminopyralid in food and water are
summarized in Table 4.

Table 4.  Chronic Aggregate Dietary (Food + Drinking Water) Exposure and
Risk for Aminopyralid

Population Subgroup	 Exposure

(mg/kg/day)	% cPAD

General U.S. Population	0.000703	<1

All Infants (< 1 year old)	0.001081	<1

Children 1-2 years old	0.002097	<1

Children 3-5 years old	0.001827	<1

Children 6-12 years old	0.001266	<1

Youth 13-19 years old	0.000822	<1

Adults 20-49 years old	0.000515	<1

Adults 50+ years old	0.000359	<1

Females 13-49 years old	0.000516	<1

VII.	Characterization of Inputs/Outputs

These chronic dietary exposure and risk estimates are highly
conservative.  They are based on the assumption that 100% of crops with
tolerances are treated with aminopyralid, and that residues in foods
“as eaten” are present at tolerance levels.  In addition, drinking
water exposure estimates are screening level estimates generated by the
Tier 1 FIRST Model.

Dietary exposure estimates could be refined through the use of
anticipated residues, percent crop treated data, and/or refined
estimated drinking water concentrations.  However, as estimated
exposures and risks using conservative assumptions are well below
HED’s level of concern, no refinements are needed at the present time.

VIII.	Conclusions

This unrefined chronic dietary exposure analysis using DEEM-FCID™
indicates that chronic dietary exposure of humans to aminopyralid from
food and drinking water is well below HED’s level of concern. 
Estimated chronic dietary exposures are less than 1% of the cPAD for the
general U.S. population and all population subgroups.  This assessment
is unlikely to underestimate risk.

IX.		List of Attachments

1.  Aminopyralid Chronic Dietary Residue Input File 

2.  Results of Aminopyralid Chronic Dietary Exposure Analysis

Attachment 1:  Aminopyralid Chronic Dietary Residue Input File

Chronic NOAEL: 50 mg/kg bw/day

Chronic PAD (cPAD):  0.50 mg/kg bw/day

DEEM FCID (Version 2.03), 1994-1996 data and 1998 Supplemental
Children’s Survey

Filename: C:\Documents and Settings\ddotson\My
Documents\Deemfcid\Aminopyralid\AminopyralidCHR.R98

Date created/last modified: 09-15-2009/16:34:553/8

------------------------------------------------------------------------
--------

  EPA    Crop                                   Def Res     Adj.Factors 
 Comment

  Code    Grp  Commodity Name                    (ppm)       #1    #2   

-------- ---- -------------------------------  ----------  ------ ------
 -------

15001200 15   Corn, field, flour                 0.200000   1.000  1.000
 

15001201 15   Corn, field, flour-babyfood        0.200000   1.000  1.000
 

15001210 15   Corn, field, meal                  0.200000   1.000  1.000
 

15001211 15   Corn, field, meal-babyfood         0.200000   1.000  1.000
 

15001220 15   Corn, field, bran                  0.200000   1.000  1.000
 

15001230 15   Corn, field, starch                0.200000   1.000  1.000
 

15001231 15   Corn, field, starch-babyfood       0.200000   1.000  1.000
 

15001240 15   Corn, field, syrup                 0.200000   1.500  1.000
 

15001241 15   Corn, field, syrup-babyfood        0.200000   1.500  1.000
 

15001250 15   Corn, field, oil                   0.200000   1.000  1.000
 

15001251 15   Corn, field, oil-babyfood          0.200000   1.000  1.000
 

15004010 15   Wheat, grain                       0.040000   1.000  1.000
 

15004011 15   Wheat, grain-babyfood              0.040000   1.000  1.000
 

15004020 15   Wheat, flour                       0.040000   1.000  1.000
 

15004021 15   Wheat, flour-babyfood              0.040000   1.000  1.000
 

15004030 15   Wheat, germ                        0.040000   1.000  1.000
 

15004040 15   Wheat, bran                        0.100000   1.000  1.000
 

21000440 M    Beef, meat                         0.020000   1.000  1.000
 

21000441 M    Beef, meat-babyfood                0.020000   1.000  1.000
 

21000450 M    Beef, meat, dried                  0.020000   1.920  1.000
 

21000460 M    Beef, meat byproducts              0.020000   1.000  1.000
 

21000461 M    Beef, meat byproducts-babyfood     0.020000   1.000  1.000
 

21000470 M    Beef, fat                          0.020000   1.000  1.000
 

21000471 M    Beef,fat-babyfood                  0.020000   1.000  1.000
 

21000480 M    Beef, kidney                       0.300000   1.000  1.000
 

21000490 M    Beef, liver                        0.020000   1.000  1.000
 

21000491 M    Beef, liver-babyfood               0.020000   1.000  1.000
 

23001690 M    Goat, meat                         0.020000   1.000  1.000
 

23001700 M    Goat, meat byproducts              0.020000   1.000  1.000
 

23001710 M    Goat, fat                          0.020000   1.000  1.000
 

23001720 M    Goat, kidney                       0.300000   1.000  1.000
 

23001730 M    Goat, liver                        0.020000   1.000  1.000
 

24001890 M    Horse, meat                        0.020000   1.000  1.000
 

26003390 M    Sheep, meat                        0.020000   1.000  1.000
 

26003391 M    Sheep, meat-babyfood               0.020000   1.000  1.000
 

26003400 M    Sheep, meat byproducts             0.020000   1.000  1.000
 

26003410 M    Sheep, fat                         0.020000   1.000  1.000
 

26003411 M    Sheep, fat-babyfood                0.020000   1.000  1.000
 

26003420 M    Sheep, kidney                      0.300000   1.000  1.000
 

26003430 M    Sheep, liver                       0.020000   1.000  1.000
 

27002220 D    Milk, fat                          0.030000   1.000  1.000
 

27002221 D    Milk, fat - baby food/infant for   0.030000   1.000  1.000
 

27012230 D    Milk, nonfat solids                0.030000   1.000  1.000
 

27012231 D    Milk, nonfat solids-baby food/in   0.030000   1.000  1.000
 

27022240 D    Milk, water                        0.030000   1.000  1.000
 

27022241 D    Milk, water-babyfood/infant form   0.030000   1.000  1.000
 

27032251 D    Milk, sugar (lactose)-baby food/   0.030000   1.000  1.000
 

86010000 O    Water, direct, all sources         0.001937   1.000  1.000
 

86020000 O    Water, indirect, all sources       0.001937   1.000  1.000
 

Attachment 2:  Results of Aminopyralid Chronic Dietary Exposure
Analysis

Chronic NOAEL: 50 mg/kg bw/day

Chronic PAD (cPAD):  0.50 mg/kg bw/day

Adjustment factor #2 NOT used.

Residue file name: Aminopyralid\AminopyralidCHR.R98

Analysis Date 09-15-2009/16:35:19    Residue file dated:
09-15-2009/16:34:55/8

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

                    Total exposure by population subgroup

------------------------------------------------------------------------
-------

                                                    Total Exposure

                                        
-----------------------------------

          Population                         mg/kg             Percent
of   

           Subgroup                       body wt/day             Rfd   
   

--------------------------------------   -------------      
---------------

U.S. Population (total)                     0.000703                
0.1%

U.S. Population (spring season)             0.000709                
0.1%

U.S. Population (summer season)             0.000716                
0.1%

U.S. Population (autumn season)             0.000699                
0.1%

U.S. Population (winter season)             0.000688                
0.1%

Northeast region                            0.000651                
0.1%

Midwest region                              0.000753                
0.2%

Southern region                             0.000681                
0.1%

Western region                              0.000732                
0.1%

Hispanics                                   0.000820                
0.2%

Non-hispanic whites                         0.000686                
0.1%

Non-hispanic blacks                         0.000715                
0.1%

Non-hisp/non-white/non-black                0.000669                
0.1%

All infants (< 1 year)                      0.001081                
0.2%

Nursing infants                             0.000319                
0.1%

	

	

 

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Non-nursing infants                         0.001370                
0.3%

Children 1-6  yrs                           0.001877                
0.4%

Children 7-12 yrs                           0.001208                
0.2%

Females 13-19 (not preg or nursing)         0.000705                
0.1%

Females 20+ (not preg or nursing)           0.000421                
0.1%

Females 13-50 yrs                           0.000568                
0.1%

Females 13+ (preg/not nursing)              0.000598                
0.1%

Females 13+ (nursing)                       0.000603                
0.1%

Males 13-19 yrs                             0.000937                
0.2%

Males 20+ yrs                               0.000494                
0.1%

Seniors 55+                                 0.000354                
0.1%

Children 1-2 yrs                            0.002097                
0.4%

Children 3-5 yrs                            0.001827                
0.4%

Children 6-12 yrs                           0.001266                
0.3%

Youth 13-19 yrs                             0.000822                
0.2%

Adults 20-49 yrs                            0.000515                
0.1%

Adults 50+ yrs                              0.000359                
0.1%

Females 13-49 yrs                           0.000516                
0.1%

------------------------------------------------------------------------
-------

Aminopyralid                                       Dietary Exposure and
Risk Assessment                           DP Number: 369212

PC Code:  005100                 		

________________________________________________________________________
____________________

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