Aminopyralid Dieta r y Exposure and Risk Assessment DP Number: 3 6 9212

PC Code: 005100

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Page 1 of 9 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460
OFFICE OF PREVENTION, PESTICIDES AND TOXIC SUBSTANCES

MEMORANDUM D ate: 10 / 2 2 /2009 SUBJECT: Aminopy

ralid Chronic Aggregate Dietary (Food and Drinking Water) Exposure and Risk Assessment for the Sec tion 3 Registration on Field Corn
PC Code: 005100 DP Number : D36 9212 Decision No : 40 1475 Registration No : 62 7 19
- 519 Petition Nos.: 8F74 55 Regulatory Action: Section 3 Registration Risk Assess Ty

pe: None Case No.: None T XR No.: None CAS No.: 566191
- 89
- 7 MRI D No.: None 40 CFR: 180. 610

FROM: Douglas Dotson, Ph.D., Chemist

Risk Assessme nt Branch II Health Effects Division (7509P) THROUGH: Donna Davis , Chem ist

William Cutchin , Chemist Dietary Exposure Science Advisory Council Health Effects Division (7509P) TO: Ka thr y

n Montague/Joanne Miller , RM Team 23 He rbicide Branch Registration Division (7505P)Aminopyralid Dieta r y Exposure and Risk Assessment DP Number: 3 6 9212

PC Code: 005100

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Page 2 of 9 Executive Summary A chronic aggregate dietary (food and drinking water ) exposure and risk assessment w as conducted for the herbicide, aminopy ralid , using the Dietary

E xposure Evaluation Model , DEEM
- FCIDTM, Version 2.03 , which use s food consumption data from the U.S. Department of Agriculture’s Continuing Survey s of Food Intakes by I ndividuals (CSFII) . The survey s were taken from 1994
- 1996 and included a supplemental children’s survey taken in 1 9 98. The anal ys is was performed to support a Section 3 tolerance petition for the use of aminopy ralid on field corn. An acute dietary assessment was not performed, a s a toxicological endpoint attributable to a single dose has not b een identified for amino py ralid
. Aminopy

ralid 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 assum ption 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. DEEMTM Version 7.81 default processing factors were applied to all processed commodities for which they were available
. Drinking water was incorporated d irectl y into the dietary assessment using the estimated drinking water concentration (EDWC) for surface water generated by the T ier 1 FQPA Index Reservoir Screening Tool ( FIRST ) M odel. The resulting chronic dietary exposure estimates for food and water co mbined 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 0.000 70 3 mg/kg/day for the U.S. population ( <1 % of the chronic population adjusted do se ( cPAD ) ) and 0.00 2 097 mg/kg/day ( <1 % of the cPAD) for children 1 to 2 ye ars old, the population subgroup with the highest estimated chronic dietary exposure to aminopy ralid
. I. Introduction Dietary risk assessment incorporates both exposure and toxic ity 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 th e population adjusted dose (PAD). The PAD is equiva lent to the point of departure (P o D; e.g. NOAEL, LOAEL, etc .) divided b y the required uncertaint y or safet y factors. For acute and non
- cancer chronic exposures, HED is concerned when estimated dietary ri sk exceeds 100% of the PAD. References which discuss the acute and chronic risk assessments in more detail are available on the EPA/pesticides w ebsite: “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 ).Aminopyralid Dieta r y Exposure and Risk Assessment DP Number: 3 6 9212

PC Code: 005100

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Page 3 of 9 II. Residue Information Residues of Concern: The nature of the residue of aminopy ralid in plants and livestock has been adequatel y delineated based on metabo lism studies conducted with aminopy ralid in wheat, grass , lactating goat s, and lay ing hen s . In metabolism studies reflecting foliar applications to grass and wheat, aminop yralid 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 aminopy ralid. HED concluded that the residues of conc ern in grass and small grain commodities are free and conjugated aminopy ralid. M etabolism studies in lactating goats and lay ing hens show that most of the administered dose is rapidly excreted (~80% for hens and ~95% for goat). T he weight of the evidence is that the limited amount of aminopy ralid that is not excreted remains as the parent compound. Therefore, the residue of concern in livestock is aminopy ralid ( Memo, D360 100 , D. Dotson , 10 / 22 /2009 ). Tolerances: Permanent tolerances have been establishe d under 40 CFR §180. 610 (a) for free and conjugated residues of aminopy ralid in or on grass and wheat commodities at levels ranging from 0.0 4 ppm in wheat grain to 50 ppm in grass hay
. Permanent tolerances have also been established residues of aminopy rali d 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 by products (except kidney ) of cattle, goat, horse, and sheep (0.02 ppm). Dow AgroSciences has proposed tolerances for residues of aminopy ralid 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 , D 360 100 , 10 / 22 /2009 )
. The tolerances are lis ted 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
Livestoc k: Livestock feedstuffs associated with the proposed uses include field corn grain, forage , silage, stover , and milled by products . Tolerances are currentl y in effect for animal commodities. Based on recalculated dietary burdens and the results of rumina nt and poultry feeding studies, HED concluded that no changes need to be made to the animal commodity tolerances. Residue Data used for the Chronic Assessment: The unrefined chronic dietary assessment is based on the assum ption that aminopy ralid residues are present at tolerance levels in all commodities for which tolerances have been established and that 100% of those crops areAminopyralid Dieta r y Exposure and Risk Assessment DP Number: 3 6 9212

PC Code: 005100

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Page 4 of 9 treated. D EEMTM Version 7.81 default processing factors were applied to all processed commodities for which they were available
. The only p rocess ed commodities in this assessment are corn s yrup and dried beef. Processing studies for these two commodities were not s ubmitted by the registrant.
III. 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 , D3 61926 , 7 /2 4 /2009 ) . W ater residues were incorporate d directl y in to 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 aminopy ralid ( Memo, D301689, M. Dohert y, 7 / 12 / 2005 ). EFED estimated residues of aminopyralid in surface water and groundwater using the FIRST and SCIGROW (Screening Concentrations in Groundwater) models, respectivel y. The model s and their description s are available at the EPA internet site: 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 E DWC (ppb) Maximum Ground Water Acute/Chronic EDWC (ppb) Acute Value Chronic/Cancer Value 10.024 1 .937 0.6 30 The chronic surface water EDWC was higher than the groundwater EDWC; therefore, the surface water value of 1 .937 ppb was used in the c hr onic 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 aminopy ralid
. IV. DEEM - FCID TM Program and Consumption Information A n aminopy

ralid chro nic dietary

exposure assessment w as conducted using the Dietary Exposure Evaluation Model software with the Food Commodity I ntake Da tabase DEEM
- FCIDTM, Version 2.03 , which incorporates consumption d ata from USDA’s Continuing Survey s of Food Intakes by I ndividuals (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 day s. Foods “as consumed” (e.g., app le 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 publicl yAminopyralid Dieta r y Exposure and Risk Assessment DP Number: 3 6 9212

PC Code: 005100

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Page 5 of 9 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 analy sis of the 1994
- 96, 98 CSFII consumption dat a, 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 y ear old), children 1
- 2, children 3
- 5, childre n 6
- 12, y outh 13
- 19, adults 20
- 49, females 13
- 49, and adults 50+ y ears 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 dail y 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 commodi ty residue list to arrive at the total average estimated exposure. Exposure is expressed in mg/kg bod y weight/day and as a percent of the cPAD. This procedure is performed for each population subgroup. V. Toxicological Information Reference : Aminopy

r alid. 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 aminopy

ralid and determined that the following endpoints and doses are appropriat e for use in the dietary risk assessment: Table 3. Summary of Toxicological Doses and Endpoints for Am inopyralid for Use in

Dietary Hum an Health Risk Assessments Exposure/ Scenario Point of

Departure Uncertainty/

FQPA Safety Factors RfD, PAD,

Level of C oncern for Risk Assessment Study and Toxicological Effects

Ac ute 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; theref

ore, an acute endpoint has not been identified.
Chronic Dietary (All Populations) NOAEL= 50

mg/kg/day UF A = 10 x

UF H =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 ba sed on c ecal 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 adequ ate rodent carcinogenicity studies.Aminopyralid Dieta r y Exposure and Risk Assessment DP Number: 3 6 9212

PC Code: 005100

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Page 6 of 9 Point of Departure (P o D) = 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 rel evant 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. N/A = not applicable. The FQPA S afet y F actor has been reduced to 1 x for all population subgroups for th e following reasons: 1) there is no e vidence of increased pre
- and/or post
- natal sensitivity / susceptibility to aminopy ralid , 2) t here is no evidence of neurotoxicity in the database (so a developmental neurotoxicity

(DNT) study

has not been required ), an d 3) the exposure values that are used in the risk assessment are conservative and are unlikel y t o underestimate risk. VI. Results/Discussion As stated above, for chronic assessments, HED is concerned when dietary risk exceeds 100% of the c PAD. The DEE M
- FCI DTM anal ys es 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 y ear old), children 1
- 2, children 3
- 5, children 6
- 12, y outh 13
- 19, females 13
- 49, adults 20
- 49, and adults 50+ years. Aminopy ralid chronic dietary

(food + water) exposure estimates using the DEEM
- FCIDTM 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 0.000 70 3 mg/kg/day for the U.S. population (<1% of the cPAD) and 0.00 2 097 mg /kg/day (<1% of the cPAD) for the most highly exposed population subgroup (children, 1
- 2 y ears old). The estimated exposures and risks f rom residues of aminopy

ralid in food and water are summarized in Table 4
. Table 4 . Chronic Aggregate Dietary (Food + Drinking Water) Exposure and Risk for Am inopyralid Population Subgroup Exposure (m g/kg/day) % cPAD General U.S. Population 0.000 70 3 <1 All Infants (< 1 year old) 0.00 1081 <1 Children 1 - 2 years old 0.00 209 7 <1 Children 3
- 5 y ears old 0.00 1 82 7 <1 Children 6
- 12 y ears old 0.00 126 6 <1 Youth 13
- 19 y ears old 0.000 822 <1 Ad ults 20
- 49 y ears old 0.000 515 <1 Ad ults 50+ years old 0.000 35 9 <1 Fem ales 13
- 49 years old 0.000 516 <1Aminopyralid Dieta r y Exposure and Risk Assessment DP Number: 3 6 9212

PC Code: 005100

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Page 7 of 9 VII. Characterization of Inputs/Outputs These chronic dietary

exposure and risk estimates are highl y conservative
. T hey are based on the assum ption that 100% of crops with tolerances are treated with aminopy ralid , and that residu es in foods “ as eaten ” are present at tolerance levels. In addition, d rinking water exposure estimates are screening level estimates generated by the T ier 1 FI RST M odel. Dietary exposure estimates could be refined through the use of anticipated residues , percent crop treated data, and/or refined estimated drinking water concentrations. However, a s estimated exposures and risks using conservative assumptions are well below HED’s level of concern, no refin ement s are needed at the present time
. VIII. Conc lusions This unrefined chronic dietary exposure analy sis using DEEM
- FCIDTM indicates that chronic dietary exposure of humans to aminopy ralid from food and drinking water is well below HED’s level of concern. Estimated chronic dietary exposures are less th an 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. A minopy

ralid Chronic Dietary

Residue Input File 2. Results of A minopy

ralid Chronic Dietary Exposure Anal ys isAminopyralid Dieta r y Exposure and Risk Assessment DP Number: 3 6 9212

PC Code: 005100

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Page 8 of 9 Attachment 1: Aminopyralid Chronic Dietary Residue I nput 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: \ Documen ts and Settings \ ddotson \ My Documents \ Deemfcid

\ Ami nopyralid

\ AminopyralidCHR .R98 Date created/last modified: 09
- 15
- 2009/ 16 : 34 : 55 3/8

-------------------------------------------------------------------------------- EPA Crop Def Res Adj.Factors Comment Code Grp Commodity Name (ppm) #1 #2

-------- ---- ------------------------------- ---------- ------ ------ ------- 15001200 15 Corn, field, flour 0.200000 1.0 00 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 150040 10 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. 10 0000 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 0.3000 00 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 Mi lk, 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 0.0019 37 1.000 1.000 86020000 O Water, indi rect, all sources 0.001937 1.000 1.000Aminopyralid Dieta r y Exposure and Risk Assessment DP Number: 3 6 9212

PC Code: 005100

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Page 9 of 9 Attachment 2: Results of Aminopy ralid Chronic Dietary

Exposure Anal ys is Chronic NOAEL: 50 mg/kg bw/day Chronic PAD (cPAD): 0. 50 mg/kg bw/day Adjustment factor #2 NOT used. Residue file name: Aminopy ralid \ Aminopy

ralid C HR .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 Percen t of Subgroup body wt/day Rfd

-------------------------------------- ------------- --------------- U.S. Population (tot al) 0.000703 0.1% U.S. Population (sp r ing season) 0.000709 0.1% U.S. Population (summer season) 0.000716 0.1% U.S. Population (aut umn 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 regi on 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/n on - black 0.000669 0.1% All infants (< 1 year) 0.001081 0.2% Nursing infants 0.000319 0.1% 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 p reg or nursin g) 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/no t 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%

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