Document ID: EPA-HQ-OPP-2010-0102-0006
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2011-04-22T04:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

 

OFFICE OF CHEMICAL SAFETY AND

                                                                        
                      POLLUTION PREVENTION

MEMORANDUM

DATE:  	February 17, 2011

SUBJECT:	Triflusulfuron-methyl: Chronic Aggregate Dietary Exposure (Food
and Drinking Water) and Risk Assessment for the Section 3 Registration
on Garden Beet

PC Code:  129002	DP Barcodes: D376268

Decision No.: 425459	Registration No.:  352-569

Petition No.:  9E7669	Regulatory Action:  Section 3 Registration

Risk Assessment Type:  Single Chemical Aggregate, Dietary	Case No.:  NA

TXR No.:  NA	CAS No.: 126535-15-7

MRID No.:  NA	40 CFR:  §180.492 

		              				

REVIEWER:	Elizabeth Holman, Chemist

Risk Assessment Branch II  (RAB2)

Health Effects Division (HED; 7509P)

THROUGH:	Debra Rate, Ph.D., Biologist

David Soderberg, Chemist

Dietary Exposure Science Advisory Council

Health Effects Division (HED; 7509P)

and

Richard Loranger, Ph.D., Branch Senior Scientist

Risk Assessment Branch II (RAB2)

Health Effects Division (HED; 7509P)

TO:		Laura Nollen, Risk Manager Reviewer

		Barbara Madden, Review Manager #5

		Daniel (Dan) Rosenblatt, Chief

Risk Integration, Minor Use, and Emergency Response Branch

		Registration Division (7505P)

Executive Summary

™, Version 2.03), which uses food consumption data from the U.S.
Department of Agriculture (USDA’s) Continuing Surveys of Food Intakes
by Individuals (CSFII) from 1994-1996 and 1998.  The analysis was
performed to support a Section 3 registration for use of
triflusulfuron-methyl [methyl
2-[[[[[4-(dimethylamino)-6-(2,2,2-trifluoroethoxy)-1,3,5-triazin-2-yl]am
ino]carbonyl]amino]sulfonyl]-3-methylbenzoate] on garden beets. 
Triflusulfuron-methyl is currently registered for use on sugar beets and
chicory.  

Acute Dietary Exposure (Food and Drinking Water) Results and
Characterization

No appropriate endpoint attributable to a single dose was identified. 
As no acute dietary endpoint was identified, an acute exposure analysis
was not performed.

Chronic Dietary (Food and Drinking Water) Exposure Results and
Characterization

The chronic analysis is based on tolerance level residues and 100% crop
treated assumptions.  The HED-recommended tolerance level for each raw
agricultural commodity (RAC) was entered as listed below: 

 

Beet, garden, roots	0.01 ppm

Beet, garden, tops	0.02 ppm

Additionally, the existing tolerances for sugar beet (roots and tops)
and chicory were also entered (a value of 0.05 ppm for each commodity). 
The general U.S. population and all population subgroups have risk
estimates that are well below HED’s level of concern (i.e., 100% of
the chronic population adjusted dose (cPAD)).  Estimated exposures are
less than 1% of the cPAD for the U.S. population and all population
subgroups, including those of infants and children.

Cancer Dietary (Food and Drinking Water) Exposure Results and
Characterization

Triflusulfuron-methyl is a Group C (1986 Cancer Guidelines - possible
human carcinogen) chemical, based on increased incidence of testicular
cell adenomas in rats.  The chronic RfD is considered adequately
protective of these effects and a quantitative cancer risk assessment
using a cancer potency factor 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 population adjusted dose
(PAD).  The PAD is equivalent to the 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.  HED is generally
concerned when estimated cancer risk exceeds one in one million. 
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,”
6/21/2000, web link: 
http://www.epa.gov/fedrgstr/EPA-PEST/2000/July/Day-12/6061.pdf ;  or see
SOP 99.6 (8/20/99).



A dietary risk assessment for triflusulfuron-methyl on sugar beet was
completed in 2000 (D260469, M.Doherty, 8/28/2000).  This assessment is
for the new proposed use on garden beet, which also incorporates the
existing uses on sugar beet and chicory.  Chicory was not included in
the 2000 dietary assessment.  

II.	Residue Information

Triflusulfuron-methyl is a sulfonylurea herbicide that inhibits the
biosynthesis of branched-chain amino acids in plants (via inhibition of
the plant enzyme acetolactate synthase).  The herbicide is currently
registered for food uses on sugar beet and chicory.

The petitioner has proposed a new Section 3 use on garden beets.  See
Table 1 below for a summary of the HED-recommended tolerances. 

Table 1.  Summary of HED- Recommended Tolerances for Proposed New Use.

Commodity	Recommended Tolerance (ppm)

Beet, garden, roots	0.01

Beet, garden, tops 	0.02

For both the existing and proposed uses, triflusulfuron-methyl parent
serves as an adequate measure of misuse based on its percentage of the
total radioactive residues (TRR) in the metabolism studies and the
residues seen in crop field trials.  

HED is making the conservative assumption of 100% crop treated.

In a previously submitted processing study for sugar beet, even at
exaggerated rates (8X) for the field trial used to generate the
processing study samples, no triflusulfuron-methyl was found in the
sugar beet roots or processed commodities (MRID 42496869; see 6/7/93 G.
J. Herndon review, D184250).  Therefore, processed commodities of sugar
beet were conservatively estimated to have tolerance-level residues of
the raw agricultural commodity of sugar beet.  

III.  Drinking Water Data

™ into the food categories “water, direct, all sources” and
“water, indirect, all sources.”   

The EDWCs are based on the maximum application rates specified in the
product label for the existing use on sugar beet.  The registrant is
proposing the new use of the chemical on garden beets.  Based on an
inspection of the new use of triflusulfuron-methyl, it was found that
sugar beet still represents the scenario with the highest exposure.  The
previously modeled use covers the new use.  Therefore, the drinking
water assessment results do not change from the previous ones.  For
electronic copy of the previous drinking water assessment refer to DP
Barcode D260078.  

Surface water estimates were calculated using the Tier II Pesticide Root
Zone Model (PRZM, v3.12.2, 5/12/2005) and the Exposure Analysis Modeling
System (EXAMS, v2.98.4.6, 4/25/2005).  These simulation models are
coupled to generate daily exposures and 1-in-10 year estimated drinking
water concentrations of triflusulfuron-methyl residues that may occur in
surface water bodies adjacent to application sites receiving
triflusulfuron-methyl through runoff and spray drift.  Groundwater
estimates were calculated using the Screening Concentration in Ground
Water (SCI-GROW v2.3, Jul. 29, 2003) regression model.  These 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 EDWCs for the human health risk assessment are presented in Table 2.
 RAB2 has selected the most conservative estimate in order to be
sufficiently protective of human health.  The maximum estimate of 0.50
ppb comes from the groundwater (SCI-GROW) estimate and was used in the
chronic dietary analysis.  

Table 2.  Estimated Drinking Water Concentrations (EDWCs) for Human
Health Risk Assessment for Aerial Application of Triflusulfuron-Methyl
on Sugar Beets.

Chemical	

Chronic Surface Water  PRZM/EXAMS (ppb)	

Acute and Chronic Ground Water  SCI-GROW (ppb)*

Triflusulfuron-methyl	0.005	0.50

IV.	DEEM-FCID( Program and Consumption Information

A triflusulfuron-methyl chronic dietary exposure assessment was
conducted using the DEEM-FCID(, Version 2.03, which incorporates
consumption data from USDA’s 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

The Health Effects Division (HED) has evaluated the toxicology database
for triflusulfuron-methyl.  The RAB2 risk assessment team reviewed the
toxicology data for triflusulfuron-methyl with regard to the acute and
chronic reference doses and the toxicological endpoint selection.  Table
3 below provides a summary of the doses and endpoints recommended for
use in the dietary exposure assessments.    SEQ CHAPTER \h \r 1
Triflusulfuron-methyl is a Group C (1986 Cancer Guidelines - possible
human carcinogen) chemical, based on increased incidence of testicular
cell adenomas in rats.  The chronic RfD is considered adequately
protective of these effects and a quantitative cancer risk assessment
using a cancer potency factor is not required.  The FQPA safety factor
was reduced to 1x for all exposure scenarios.  

Table 3.  Summary of Toxicological Doses and Endpoints for
Triflusulfuron-Methyl for Use in Dietary and Non-Occupational 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 age 13 to 49)	Not required.  An appropriate endpoint for this
risk assessment was not identified.

Chronic Dietary (All Populations)	NOAEL= 2.44  mg/kg/day	UFA= 10x

UFH= 10x

FQPA SF= 1x   	Chronic RfD = 0.0244

mg/kg/day

cPAD = 0.0244 mg/kg/day	Chronic oral toxicity/carcinogenicity in the rat

LOAEL = 30.6 mg/kg/day, based on decreased body weight/weight gain,
hematological changes (primarily males) and increased interstitial cell
hyperplasia (males).

Cancer (oral, dermal, inhalation)	Classification:  Group C (1986 Cancer
Guidelines), based on increased incidence of testicular interstitial
cell adenomas in rats.   The chronic RfD is considered adequately
protective of these effects and a quantitative assessment of cancer risk
using a cancer potency factor is not required.

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.  MOE =
margin of exposure.  LOC = level of concern. 

VI.	Results/Discussion

As stated above, for acute and chronic assessments, HED is concerned
when dietary risk exceeds 100% of the PAD.  The DEEM-FCID( analysis
estimates the dietary exposure of the U.S. population and various
population subgroups.  The results reported in Table 5 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.

Results of Acute Dietary (Food and Drinking Water) Exposure Analysis

No appropriate endpoint attributable to a single dose was identified. 
As no acute dietary endpoint was identified, an acute exposure analysis
was not performed.

Results of Chronic Dietary (Food and Drinking Water) Exposure Analysis

The summary table below lists the results of the chronic dietary
exposure analysis.  Estimated chronic dietary risk estimates are less
than 1% of the cPAD for the U.S. population and all population
subgroups, including those of infants and children.  Thus, all
population exposures are well below HED’s level of concern.   



Table 4.  Summary of Dietary Exposure and Risk for
Triflusulfuron-Methyl.

Population Subgroup*	

Acute Dietary	

Chronic Dietary	

Cancer

	

Dietary Exposure (mg/kg/day)	

% aPAD	

Dietary Exposure

(mg/kg/day)	

% cPAD	

Dietary Exposure

(mg/kg/day)	

Risk

General U.S. Population	N/A

No acute dietary endpoint was identified	N/A	0.000025	<1%	

N/A	

N/A

All Infants (< 1 year old)

	0.000050   	<1%

Children 1-2 years old

	0.000052	<1%

Children 3-5 years old

	0.000056	<1%

Children 6-12 years old

	0.000041	<1%

Youth 13-19 years old

	0.000023	<1%

Adults 20-49 years old

	0.000020	<1%

Adults 50+ years old

	0.000019	<1%

Females 13-49 years old

	0.000021	<1%

VII.	Characterization of Inputs/Outputs

As the exposure estimates to all population subgroups were so low, it
was not necessary to make refinements to the chronic dietary analysis. 
If it had been necessary to refine the analysis, average field trial
values could have been used in place of tolerance level residues.  In
addition, estimates of percent crop treated could have been used.

VIII.	Conclusions

Based on very conservative assumptions, the chronic dietary risk
estimates are well below HED’s level of concern for the general U.S.
population and all population subgroups, including those comprised of
infants and children.  In addition, cancer risk from dietary exposure to
triflusulfuron-methyl is not of concern to HED (the cRfD is protective
of cancer effects).  Based on the conservative nature of the chronic
dietary endpoint and the drinking water assessment, exposure and risk to
triflusulfuron-methyl are not expected to be underestimated.  

IX.	List of Attachments

Attachment 1: Residue Input File for Chronic Analysis

Attachment 2: Results of Chronic Dietary Exposure Analysis

Attachment 1:  Triflusulfuron-methyl Residue Input File

Filename: F:\Triflusulfuron\Dietary\Triflusulfuron-methyl Chronic
final.R98

Chemical: Triflusulfuron-methyl

RfD(Chronic): .0244 mg/kg bw/day  NOEL(Chronic): 2.44 mg/kg bw/day

RfD(Acute): 0 mg/kg bw/day  NOEL(Acute):  0 mg/kg bw/day

Date created/last modified: 02-17-2011/09:08:08/8          Program ver.
2.03

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

  EPA    Crop                                   Def Res     Adj.Factors 
 Comment

  Code    Grp  Commodity Name                    (ppm)       #1    #2   

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

86010000 O    Water, direct, all sources         0.000500   1.000  1.000
 

86020000 O    Water, indirect, all sources       0.000500   1.000  1.000
 

01010500 1AB  Beet, garden, roots                0.010000   1.000  1.000
 

01010501 1AB  Beet, garden, roots-babyfood       0.010000   1.000  1.000
 

01010520 1A   Beet, sugar                        0.050000   1.000  1.000
 

01010521 1A   Beet, sugar-babyfood               0.050000   1.000  1.000
 

01010530 1A   Beet, sugar, molasses              0.050000   1.000  1.000
 

01010531 1A   Beet, sugar, molasses-babyfood     0.050000   1.000  1.000
 

01011000 1AB  Chicory, roots                     0.050000   1.000  1.000
 

02000510 2    Beet, garden, tops                 0.020000   1.000  1.000
 

02001010 2    Chicory, tops                      0.050000   1.000  1.000
 

  

Attachment 2:  Results of Triflusulfuron-methyl Chronic Dietary
Exposure Analysis

U.S. Environmental Protection Agency                                
Ver. 2.00

DEEM-FCID Chronic analysis for TRIFLUSULFURON-METHYL            (1994-98
data)

Residue file name: F:\Triflusulfuron\Dietary\Triflusulfuron-methyl
Chronic final.R98

                                                     Adjustment factor
#2 used.

Analysis Date 02-17-2011/09:16:12     Residue file dated:
02-17-2011/09:08:08/8

Reference dose (RfD, Chronic) = .0244 mg/kg bw/day

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

                    Total exposure by population subgroup

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

                                                    Total Exposure

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

          Population                         mg/kg             Percent
of   

           Subgroup                       body wt/day             Rfd   
   

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

U.S. Population (total)                     0.000025                
0.1%

U.S. Population (spring season)             0.000026                
0.1%

U.S. Population (summer season)             0.000026                
0.1%

U.S. Population (autumn season)             0.000025                
0.1%

U.S. Population (winter season)             0.000025                
0.1%

Northeast region                            0.000024                
0.1%

Midwest region                              0.000027                
0.1%

Southern region                             0.000024                
0.1%

Western region                              0.000026                
0.1%

Hispanics                                   0.000026                
0.1%

Non-hispanic whites                         0.000025                
0.1%

Non-hispanic blacks                         0.000025                
0.1%

Non-hisp/non-white/non-black                0.000025                
0.1%

All infants (< 1 year)                      0.000050                
0.2%

Nursing infants                             0.000019                
0.1%

Non-nursing infants                         0.000061                
0.3%

Children 1-6  yrs                           0.000054                
0.2%

Children 7-12 yrs                           0.000039                
0.2%

Females 13-19 (not preg or nursing)         0.000022                
0.1%

Females 20+ (not preg or nursing)           0.000020                
0.1%

Females 13-50 yrs                           0.000022                
0.1%

Females 13+ (preg/not nursing)              0.000025                
0.1%

Females 13+ (nursing)                       0.000027                
0.1%

Males 13-19 yrs                             0.000024                
0.1%

Males 20+ yrs                               0.000019                
0.1%

Seniors 55+                                 0.000019                
0.1%

Children 1-2 yrs                            0.000052                
0.2%

Children 3-5 yrs                            0.000056                
0.2%

Children 6-12 yrs                           0.000041                
0.2%

Youth 13-19 yrs                             0.000023                
0.1%

Adults 20-49 yrs                            0.000020                
0.1%

Adults 50+ yrs                              0.000019                
0.1%

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Females 13-49 yrs                           0.000021                
0.1%

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

Triflusulfuron-methyl                             Dietary Exposure
Assessment                                      DP Barcode: D376268

PC Code: 129002		

	

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